ИЗМЕНЕНИЯ ПРОКАЛЬЦИТОНИНА В ПОСТТРАВМАТИЧЕСКОМ ПЕРИОДЕ И ЕГО РОЛЬ В СИСТЕМНОМ ОТВЕТЕ НА ТРАВМУ

Procalcitonin is an important marker used in the clinical practice for sepsis diagnostics. However the increase of its concentration can be registered in the early post-traumatic period with no obvious nidus of infection. Goal: to clarify the value of procalcitonin as a biomarker in those with concurrent trauma. Methods. 76 those injured were examined and divided into subgroups depending on the severity of trauma (ISS < 20 and ISS > 20 scores) and outcome (favorable, unfavorable, with infectious complications and no infectious complications). The changes in procalcitonin level in the subgroups were compared with intensity of the systemic response to the injury through changes in IL-6, IL-8, IL-10, CD14, HLA-DR, secretory immunoglobulin A. Blood was collected upon admission to hospital, in 12 hours, on the 1st, 3rd, 7th and 10th days. Results. It has been found out that in case of concurrent trauma the procalcitonin level in blood increased immediately and it was especially intensively expressed in severe trauma (ISS > 20 scores). During first 24 hours it was tens times above the normal and it remained above the normal during the post-traumatic period. And these changes were not related to a generalized infection. During all period of follow up the changes in procalcitonin level coincided with changes in the systemic inflammatory response and anti-inflammatory and pro-inflammatory cytokines though with a certain delay. Procalcitonin level did not increase repeatedly every time as nidus of infection manifested, it occurred more often in those with lethal outcome. High procalcitonin level in the acute post-traumatic period indicated higher chances of septic complications development on the 7-10th day. Conclusion. Along with the role of procalcitonin as an infection marker, changes in its concentration in the early post-traumatic period can be considered as a laboratory sign of the intensity of systemic response to the injury.Прокальцитонин – важный биомаркер, используемый в клинической практике для диагностики сепсиса. Однако в ближайшем посттравматическом периоде повышение его концентрации может регистрироваться и при отсутствии явного очага инфекции. Цель: уточнить значение прокальцитонина как биомаркера у пострадавших с сочетанной травмой. Методика. Обследовано 76 пострадавших, которых разделяли на подгруппы с учетом тяжести травмы (ISS < 20 и ISS > 20 баллов) и исхода (благоприятный, неблагоприятный, с инфекционными осложнениями или без них). Динамику концентрации прокальцитонина в подгруппах сопоставляли с выраженностью системного ответа на повреждение, изменениями IL-6, IL-8, IL-10, CD14, HLA-DR, секреторного иммуноглобулина А. Забор крови производили при поступлении, через 12 ч, на 1, 3, 7, 10-е сут. Результаты. Установлено, что при сочетанной травме повышение концентрации прокальцитонина в крови происходило сразу и особенно заметно при тяжелых (ISS > 20 баллов) повреждениях. Уже в 1-е сут она превышала нормальные значения в десятки раз и оставалась выше нормы в течение ближайшего посттравматического периода. Эти изменения не были связаны с генерализованным инфекционным процессом. На протяжении всего срока наблюдения динамика прокальцитонина, хотя и с некоторым опозданием, но совпадала с изменениями системной воспалительной реакции, а также противо- и провоспалительных цитокинов. Повторное повышение уровня прокальцитонина при манифестации очага инфекции проявлялось не всегда, чаще – у лиц с летальным исходом. Высокий уровень прокальцитонина в остром периоде после травмы указывал на большую вероятность развития септических осложнений на 7–10-е сут. Заключение. Наряду с отводимой прокальцитонину ролью биомаркера инфекции, изменения его концентрации в раннем посттравматическом периоде можно рассматривать в качестве лабораторного признака выраженности системного ответа организма на повреждение.

Aspects of risk factors, pathophysiology and outcomes in trauma

Trauma is a global health concern. Many trauma patients succumb on the scene or in the immediate phase after trauma. Patients surviving the initial phase may die at a later stage or suffer debilitating consequences in the post-resuscitation phase of trauma care in intensive care units. This thesis is focused on factors associated with outcomes and complications after trauma, as well as early recognition of these complications. Trauma patients using β-adrenergic receptor antagonists (β-blockers) at the time of injury had more comorbidities and an increased mortality compared to non-users. However, when adjusting for relevant confounders no association between pre-traumatic β-blockade and mortality survival was seen. Previous research suggesting a protective effect of β-blockers in trauma could therefore not be supported. We investigated thioredoxin (TRX), a potent endogenous antioxidant, and its associations with post-injury sepsis. TRX was elevated after an inflicted femur fracture and subsequent hemorrhage in an animal trauma model. Plasma-levels of thioredoxin was also evaluated in 83 severely injured trauma patients and were significantly higher when compared to healthy controls. This biomarker was associated with injury severity, shock on arrival and massive transfusion. Further, an association between TRX and post-injury sepsis was shown after adjustments for confounders. The new sepsis definition, sepsis-3, was evaluated and compared with the previous definition, sepsis-2, in 722 severely injured trauma patients. Fewer patients were diagnosed with sepsis when using the new sepsis-3 definition as compared with the old sepsis-2 definition. No association was seen between sepsis, regardless of definition used and overall mortality. However, after censoring patients dying on the first day, before being at risk for sepsis, sepsis-3 was associated with 30-day mortality, whereas sepsis-2 was not. The new definition was feasible and had a stronger association with mortality. Risk factors for post-injury sepsis as defined by the new sepsis-3 criteria included: age, spineand chest-injuries, shock on arrival and blood transfusion. Moreover, there was an association between blood alcohol at admission and later development of sepsis previously not described. Patients who developed post-injury sepsis had a complicated clinical course with an increased need for vasopressor treatment, mechanical ventilation and had more days with organ dysfunction. A significant association between post-injury sepsis and mortality was shown, but only after early censoring for trauma-related deaths. Using a technique for longitudinal clustering, we identified five distinct trajectories of organ dysfunction after trauma. Each one with different baseline characteristics, evolution of organ dysfunction and outcomes. These trajectories had unequal times until stabilization, indicating that some trajectories are easier to identify in an early stage. The study underlines the heterogenous course after trauma and suggests that there exist subsets of traumatically injured patients that might benefit from targeted measures

Lung-derived macrophage migration inhibitory factor in adult patients with septic shock, and its role in cardiocirculatory depression

Migration inhibitory factor (MIF), a critical proinflammatory mediator in sepsis, has a profound affect on cardiovascular function. Our animal studies show that the lungs release MIF into the systemic circulation during late sepsis. MIF released in this way has direct and immediate access to cardiac cells. The purpose of our study was to assess the lung as a source of MIF in human septic shock patients and to further study the MIF-associated pathways involved in cardiovascular depression

Significance of Biomarkers as a Predictive Factor for Post-Traumatic Sepsis

Purpose Many traumatic patients die from sepsis and multiple organ failure. Early recognition of post-traumatic sepsis in traumatic patients will help improve the prognosis. Recently, procalcitonin (PCT), macrophage migration inhibitory factor (MIF), and lactic acid have emerged as predictive factors. Our study aims to explore the significance of PCT, MIF and lactic acid as a predictor of posttraumatic-sepsis in trauma patients. Methods This study was conducted on prospective observational study patients who visited an emergency medical center in a university hospital from March 2014 to February 2016. We measured the white blood cells, c-reactive protein (CRP), lactic acid, PCT, and MIF with serum taken from the patient’s blood within 1 hour of the occurrence of the trauma. The definition of post-traumatic sepsis was defined as being part of systemic inflammation response syndrome criteria with infections within a week. Results A total of 132 patients were analyzed, wherein 74 patients were included in the low injury severity score (ISS) group (ISS <15) and 58 patients were included in the high ISS group (ISS ≥15). The mean PCT, MIF, and lactic acid levels were higher in the high ISS group (p<0.05). Meanwhile, 38 patients were included in the early sepsis group and 94 patients were included in the non-sepsis group. The mean MIF levels were higher in the sepsis group than the non-sepsis group (p<0.05) and there were no significant differences in the initial CRP, lactic acid, and PCT levels in these two groups. Conclusions MIF may be considered as a predictive factor for sepsis in trauma patients

Sex differences in the time trends of sepsis biomarkers following polytrauma

Sepsis is a major cause of death in polytrauma patients, with delayed antibiotics increasing mortality. Although biological sex influences immune function and disease outcomes, gender-specific differences in inflammatory response and sepsis progression remain underexplored. This study examined the time-dependent behavior of C-reactive protein (CRP), procalcitonin (PCT), and white blood cell count (WBC) in male and female polytrauma patients to evaluate their predictive value for sepsis. Additionally, it compared infection sources between genders. This retrospective cohort study at University Hospital Zurich included polytrauma patients aged ≥ 16 years with an Injury Severity Score (ISS) ≥ 16 who developed sepsis within 31 days of admission. Patients were grouped by sepsis status and gender. Time-dependent inflammatory markers (CRP, PCT, WBC) were analyzed using the Mann-Whitney U-test and binary logistic regression. The Closest Top-Left Threshold Method determined time-specific sepsis thresholds. The study i

Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction

INTRODUCTION: Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response. PATIENTS AND METHODS: One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection). RESULTS: PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12). PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann–Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP. CONCLUSIONS: PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters