The Use of Circulating miRNAs as Biomarkers for Oxidative Stress in Critically Ill Polytrauma Patients.

BACKGROUND: The diversity of primary and secondary traumatic injuries specific for the critically ill polytrauma patient is complicating the therapeutic management in the absence of a strict assessment of the biological changes. Inflammation, redox imbalance, and immunosuppression can be quantified by various biochemical parameters; however, they do not fully respond to the current requirements. Another phenomenon responsible for worsening the clinical status and for the development of complications in such patients is oxidative stress. Its aggressiveness combined with biochemical and physiological imbalances leads to increased morbidity and mortality. To minimize the effects induced by free radicals, various substances are administered with high antioxidant capacity. However, the dosage optimization for each patient is difficult without strict monitoring of oxidative stress. In this paper we will summarize and present the pathophysiology of oxidative stress, as well as the specificity of miRNAs for a series of molecular changes at the cellular level. METHODS: For this study the available literature on specific databases such as PubMed, Embase and Scopus was thoroughly analyzed. Each article has been carefully reviewed, extracting useful information for this study. The keywords used to select the relevant articles were "oxidative stress", "antioxidant therapy", "microRNAs biomarkers", and "critically ill patients". RESULTS: For this study, 121 scientific articles relevant to our topic were analyzed. Currently, quantification of oxidative stress is achieved through indirect correlations with plasma levels of specific biomarkers. For a more specific evaluation of the redox status, numerous studies were conducted on the use of circulating miRNAs as biomarkers in this regard. CONCLUSIONS: Introducing miRNAs can revolutionize both monitoring and therapy modulation in these patients, adapting to the organic damage.

Redox Changes Induced by General Anesthesia in Critically Ill Patients with Multiple Traumas.

The critically ill polytrauma patient is a constant challenge for the trauma team due to the complexity of the complications presented. Intense inflammatory response and infections, as well as multiple organ dysfunctions, significantly increase the rate of morbidity and mortality in these patients. Moreover, due to the physiological and biochemical imbalances present in this type of patients, the bioproduction of free radicals is significantly accelerated, thus installing the oxidative stress. In the therapeutic management of such patients, multiple surgical interventions are required and therefore they are being subjected to repeated general anesthesia. In this paper, we want to present the pathophysiological implications of oxidative stress in critically ill patients with multiple traumas and the implications of general anesthesia on the redox mechanisms of the cell. We also want to summarize the antioxidant treatments able to reduce the intensity of oxidative stress by modulating the biochemical activity of some cellular mechanisms.

Influence of antioxidant therapy on the clinical status of multiple trauma patients. A retrospective single center study.

INTRODUCTION: The biochemical processes of bioproduction of free radicals (FR) are significantly increasing in polytrauma patients. Decreased plasma concentrations of antioxidants, correlated with a disturbance of the redox balance are responsible for the installation of the phenomenon called oxidative stress (OS). OS action is associated with a series of secondary complications with direct implications in reducing the rate of survival, as well as in increasing morbidity The objectives of this study were to reveal possible relations between antioxidant therapy and a number of serum biochemical variables (ALT, AST, APPT, LDH, urea, leukocytes, platelets), the length of mechanical ventilation, the time spent in the ICU, and the mortality rate in major trauma patients. MATERIALS AND METHODS: In this retrospective study from a single center, 64 medical files of polytrauma patients admitted to the ICU "Casa Austria" were analysed. The selection criteria were: the Injury Severity Score (ISS) > 16 and a systolic arterial pressure (SAP) < 89 mmHg. The selected patients (n = 34) were divided into two groups: Antiox group, 20 patients who benefited from antioxidant therapy and the Contr group, 14 patients who did not received antioxidant therapy and served as a control group. The antioxidant therapy consisted of the simultaneous administration of vitamin C (i.v.), vitamin B1 (i.v.) and N-acetylcysteine (i.v.). The clinical and the biological evaluation were performed repeatedly until discharge from the ICU or the death of the patient. RESULTS: No significant differences were highlighted concerning the demographic data, the magnitude or the trauma mechanism between the two groups. In comparison with patients from the Contr group, the patients submitted to antioxidant therapy showed lower values after the treatment for leukocytes (p = 0.0066), urea (p = 0.0076), LDH (p = 0.0238), AST (p = 0.0070) and ALT (p < 0.0001). No statistically significant differences were evidenced regarding the incidence of sepsis or the development of multiple organ dysfunction syndrome (MODS). The period of mechanical ventilation was longer in patients from the Contr group (p = 0.0498), with no differences concerning the ICU length of stay (p = 0.7313). The mortality rate was lower in the Contr group (p = 0.0475). CONCLUSION: In multiple trauma patients a prolonged antioxidant therapy improved the posttraumatic laboratory tests.

Use of miRNAs as biomarkers in sepsis.

Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19-23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis.

Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma--a review.

Multiple trauma patients require extremely good management and thus, the trauma team needs to be prepared and to be up to date with the new standards of intensive therapy. Oxidative stress and free radicals represent an extremely aggressive factor to cells, having a direct consequence upon the severity of lung inflammation. Pulmonary tissue is damaged by oxidative stress, leading to biosynthesis of mediators that exacerbate inflammation modulators. The subsequent inflammation spreads throughout the body, leading most of the time to multiple organ dysfunction and death. In this paper, we briefly present an update of biochemical effects of oxidative stress and free radical damage to the pulmonary tissue in patients in critical condition in the intensive care unit. Also, we would like to present a series of active substances that substantially reduce the aggressiveness of free radicals, increasing the chances of survival.