Diminished levels of activated protein C are associated with reduced inhibition of the procoagulant factors V and VIII, as well as impaired fibrinolysis, and the infusion of recombinant human activated protein C (drotrecogin-а) has been shown to reduce mortality in patients with severe sepsis and a high risk of death, but not in those with a low risk of death based on the initial APACHE II score. In this context, the possibility of small-vessel thrombosis with subsequent myocardial microinfarction and troponin release cannot be excluded.
Interestingly, a recently published study revealed lower cTnI levels in patients with severe sepsis who had been treated with drotrecogin-а (n = 23) on day 2 of therapy compared to a similar group of patients not receiving the drug (n = 34). There was a nonsignificant trend toward lower mortality in the drotreco-gin-а group (22% vs 32%, respectively; p = 0.11). However, it remains unclear whether the smaller troponin release in the drotrecogin-а group indicates less microvascular injury with subsequently lower mortality following the therapy applied, or whether the lower cTnI levels reflect the better prognosis of the drotrecogin-а group independent of the effect of the drug. In addition, regarding the above-mentioned correlation between troponin levels and the maximal vasopressor doses administered, catecholamine toxicity has to be considered as another possible underlying mechanism. Here
There is a large body of evidence that, in patients who have been treated with maintenance hemodialysis, cardiac troponin levels can be raised even in the absence of ACS, and especially that cTnT level elevation is predictive for cardiovascular events and mortality. In addition, some investigators have found a relationship between cTnT and significant coronary atherosclerosis and left ventricular hyper-trophy, respectively. However, the exact mechanism of troponin release in patients with renal failure is still unknown.
Several studies in patients with end-stage renal failure have revealed a low specificity of cardiac troponins for the assessment of ACS, especially of cTnT, which is excreted mainly by the kidney. Similarly, we must assume that in these patients sepsis-associated cardiac troponins do not have the same predictive value for impaired LVEF and worse outcome compared to those with normal or moderately impaired renal function. However, the degree above which renal dysfunction cardiac troponins can be raised in the absence of ACS, and whether the findings from studies in patients with chronic renal failure can also be applied to those with sepsis-associated acute renal failure requiring hemodialysis or hemofiltration is currently unknown. Therefore, the cautious interpretation of elevated troponin levels in patients with significant renal dysfunction is warranted in any clinical situation.