Our study shows that the levels of hemoglobin and cardiac troponinT,(cTnT) in ICU patients with sepsis may affect the prognosis of patients, and the efficacy of multifactor combined test for sepsis assessment is better than that of a single indicator. Treatment strategies to improve the factors identified in this study may improve the inpatient survival rate of these ICU patients. cTnT was elevated in 2866 ICU sepsis patients (< 0.1ng/ml) in 47% (1356 patients), which is similar to about 40%-50% of patients with sepsis in epidemiological studies with varying degrees of troponin elevation[16]. Troponin is an important regulatory protein of striated muscle contraction. cTnT in troponin is released into the blood when myocardial cells are damaged, which is an important marker for the diagnosis of myocardial injury. cTnT can be released into the blood for 3–4 hours at the earliest and 48 hours at the latest after the occurrence of myocardial injury in sepsis[17]. Since this study only included cTnT levels for the first time after admission to ICU, the significance of the study results may be reduced. cTnT, as a sensitive marker of myocardial injury, is not specific enough to recognize septic myocardial injury in the early stage because of its elevation in patients with various etiologies. However, when the damage range of cardiomyocytes in patients with sepsis tends to be further expanded, the dynamic increase of cTnT is proportional to the degree of dynamic damage of cardiomyocytes[18]. A study shows sepsis myocardial injury and myocardial tissue energy depletion was positively related to [19], and lactic acid as the anaerobic metabolism of the body tissues and organs of microcirculation index can well response organization energy depletion, so when accompanied by lactic acid value increases, the myocardial tissue often cannot get enough energy supply, prompting development of myocardial injury and When myocardial injury occurs to a certain extent, it may lead to cardiac insufficiency, thus worsening the microcirculation of systemic tissues and further aggravating multi-organ dysfunction. Vasile et al.[20] showed that with the increase of cTnT level, the left diastolic function of patients with sepsis cardiomyopathy significantly decreased, and the incidence of cardiac dysfunction was positively correlated with the level of cTnT[21]. Such reversible cardiac function inhibition is called sepsis induced cardiomyopathy. (SICM)[22]. In septic cardiomyopathy, the increase of troponin is not due to the ischemic necrosis of large area of cardiomyocytes, but to the reversible inhibition of cardiac function caused by the energy metabolism disorders of cardiomyocytes. If the inhibition of cardiac function occurs, the risk of death of patients with sepsis will be increased [23].Different from the "high output low resistance" of normal sepsis patients, the hemodynamic characteristics of patients with sepsis cardiomyopathy are left heart dysfunction, with reduced cardiac output and thus unable to meet the needs of organ blood perfusion, which aggravating the occurrence and development of organ dysfunction. At present, the pathogenesis of myocardial injury in sepsis is not clear, some animal experiments have shown that inflammatory factors in inflammatory response [24] may be involved in the process of myocardial injury in sepsis. Hawkins et al.[25]found that an increase in neutrophils is accompanied by a decrease in lymphocytes in sepsis, and that an increase in neutrophils/lymphocytes ratio reflects the degree of sepsis inflammation. As early as 2001, Zahorec[26] suggested that neutrophils/lymphocytes ratio should be used as a predictor of infection in ICU patients. Some basic studies[27] have found that neutrophils can migrate into the myocardial interstitium after activation, thus inducing myocardial inflammation and affecting the blood flow distribution of cardiac microcirculation. In recent years, neutrophils/lymphocytes ratio has often been used as an important indicator to predict myocardial injury and heart failure[28–30]. This study has not found a relationship between WBC count and mortality in patients with sepsis, which needs further study possibly due to selection bias. The results of this study also showed that AUCROC and cut-off of troponin T for predicting nosocomial death of sepsis patients were 0.548 and 60ng/L. Bergenzaun et al.[31]found that the AUCROC and cut-off of troponin T in predicting 1-year death of severe patients was 0.76 and 117.5ng/L. The cutoff and AUCROC in this study are lower than those in the above study. The reason for this difference may be the difference in the study time endpoints. The hospital-based mortality was predicted in this study, while the 1-year mortality was predicted in the above study. Despite these differences, both indicate that troponin T levels in early ICU admission predict patient outcome.
2886 patients with septic shock were included in this study, and 759 patients had hemoglobin ≤ 90g/L, with the incidence of 26.2%. 3534 ICU patients were included in a large scale of observational study in Europe with an average hemoglobin level of 113g/L at admission, and 29% of them had hemoglobin level < 100g /L[32]. A prospective cohort study showed that 55% of patients with septic shock had hemoglobin levels < 90g /L[33]. The common causes of anemia are trauma, surgery, or occult gastrointestinal hemorrhage, which are rare in patients with septic shock. Septic shock is a complex pathophysiological process and Potential mechanisms include changes in microcirculation, decreased erythropoiesis, chronic anemia, hemodilution, and increased erythrocyte destruction due to changes in erythrocyte membrane. Current guidelines suggest that hemoglobin level < 70 g /L is one of the indications for blood transfusion to maintain hemoglobin level at 70–90 g /L in patients without myocardial ischemia, severe hypoxemia, acute hemorrhage[34]. Sepsis treatment guidelines suggest that hemoglobin < 70 g/L is the indication for transfusion, but for patients with bleeding tendency or invasive procedures, prophylactic infusion of fresh frozen plasma is feasible. However, a research showed that there was no statistically significant difference in mortality between patients with septic shock whose blood transfusion threshold was 70 g/L and 90 g/L of hemoglobin [35]. It should be noted that hemoglobin level is correlated with the amount of intravenous fluids during resuscitation[36]. In this study, mortality in patients with septic shock increased as hemoglobin levels decreased at admission and the results of multivariate regression analysis showed that hemoglobin level at admission was an independent factor influencing the death of patients with septic shock, similar to the results of Muady et al[9], suggesting that hemoglobin level at admission may be a prognostic indicator for patients with septic shock. Hemoglobin < 100 g/L was independently associated with 90-day death in patients with community-acquired pneumonia[37]. Patients with septic shock requiring red blood cell infusion may have been more severely ill originally, but there was no significant difference in mortality between the two groups [38, 39]. Other studies have shown that red blood cell infusion is associated with low mortality in patients with severe septic shock [40]. In this study, the CUT-OFF value of hemoglobin level on ROC curve was ≤ 10g/dl, which may suggest more aggressive red blood cell infusion for patients with sepsis. Although this study adopted multiple regression analysis to explore the influencing factors of death in patients with septic shock, there are still some confounding factors that cannot be measured, such as the empirical use of antibiotics. Studies have suggested that hemoglobin < 100 g/L in patients with acute coronary syndrome(ACS), the incidence of angina pectoris, heart failure and cardiogenic death after myocardial infarction was increased.This study found that sepsis patients with decreased hemoglobin levels had significantly higher in-hospital all-cause mortality than the other group. At present, there is no relevant study on the effect of hemoglobin level on the mortality of SICM patients, and the reasons for the effect of decreased hemoglobin on the prognosis of sepsis patients are complicated. First of all, when hemoglobin decreases, effective circulating blood volume and heart rate were increased to meet the oxygen supply of the whole body tissues, which further increases the oxygen consumption of the heart. Secondly, decreased hemoglobin leads to decreased blood oxygen carrying and reduced myocardial oxygen supply, aggravating the imbalance between cardiac oxygen supply and oxygen demand and increasing the incidence of adverse cardiac events in patients with sepsis [13]. We found that heart rate and respiration rate may also increase the mortality rate for patients with sepsis, because in addition to the serious condition of such patients, the increase in respiration rate and heart rate also brings about greater oxygen consumption, which increases the burden on the heart.
This study had the following limitations :(1) the time interval between the onset of sepsis and blood collection for troponin T determination was not significant; (2) There may be information bias in evaluating the prognosis of patients with troponin T level at one point in time, and the change of troponin level is not dynamically assessed; (3) Ultrasound parameters reflecting left ventricular diastolic function were not included in this study, which could not explain the relationship between cardiac function and troponin T level. (4) There are too few included variables.
In conclusion, hemoglobin and troponin levels in ICU patients with sepsis may affect the prognosis of patients, and the efficacy of multifactor combined test for the prognosis of sepsis is better than that of a single indicator. Treatment strategies to improve the factors identified in this study may improve the inpatient survival rate of these ICU patients.