102 R. Murray et al.: J Extra Corpor Technol 2025, 57, 96 – 104
Table 4. Biomarker response to infection. Biomarker
72 h before infection( Day-3)
48 h before infection( Day-2)
24 h before infection( Day-1)
Day of infection( Day 0)
|
N = 10 1 |
N = 10 1 |
N = 10 1 |
N = 7 1 |
sTREM-1( ng / L) |
555( 174, 243, 705, 1054) [ 531, 305 ] |
524( 205, 283, 849, 1092) [ 576, 332 ] |
527( 222, 309, 557, 1174) [ 540, 299 ] |
461( 228, 413, 652, 883) [ 529, 231 ] |
Presepsin( pg / mL) |
58,166( 8476, 26,168, 117,452, 1,059,987) [ 161,290, 319,011 ] |
49,313( 9627, 27,531, 72,484, 615,634) [ 102,795, 181,808 ] |
32,334( 13,051, 21,606, 57,477, 524,715) [ 85,239, 155,820 ] |
24,080( 11,008, 17,324, 54,786, 1,004,613) [ 169,132, 368,893 ] |
CRP( mg / mL) |
131( 25, 56, 288, 1016) [ 251, 314 ] |
85( 15, 35, 305, 684) [ 210, 244 ] |
186( 9, 68, 367, 500) [ 219, 189 ] |
220( 12, 75, 304, 564) [ 222, 193 ] |
PCT( ng / mL) |
1( 0, 0, 2, 189) [ 20, 59 ] |
0( 0, 0, 1, 131) [ 14, 41 ] |
0( 0, 0, 1, 72) [ 8, 23 ] |
0( 0, 0, 1, 41) [ 6, 15 ] |
Legend: 1 Median( Minimum, Interquartile Range, Maximum) [ Mean, Standard Deviation ]. Three patients did not have samples available for analysis on the day of infection due to the use of residual samples. 1 CRP value missing from Day-2 and Day-1. Day of infection represents the day the culture was obtained that developed an infection. Soluble Triggering Receptor expressed on Myeloid cells( sTREM-1), C-Reactive
The patient population of our study is representative overall of children receiving MCS, with a bias towards the Cardiac ICU, consistent with other pediatric literature [ 1 ]. The rate of infection within our biobank was 25 %( 20 / 81) which was comparable to previously reported infectious complications, ranging from 4.6 % in the neonatal MCS population to 42 % in the pediatric MCS population [ 4 ]. Additionally, our identified patient cohort had a high mortality rate( 67 %) which is consistent with previous literature demonstrating a high mortality rate in MCS patients who develop infectious complications [ 2 – 4 ].
Interestingly, the pre-cannulation values of sTREM-1( 446 ng / L in our population compared to 105 ng / L) and Presepsin( 38,630 pg / mL in our population compared to 3394 pg / mL) were higher than has been previously reported in the literature, albeit our population is slightly older than patients included in previous studies of these biomarkers which focused on primarily septic neonates, and our patients were about to be cannulated to MCS [ 6, 15, 18, 19, 29 ]. We attribute these higher levels of novel biomarkers to the illness severity faced by patients who are about to be cannulated for MCS, however there may be additional, not yet understood differences with regards to these biomarkers and how they respond in neonates compared to our slightly older population. It is also possible that given the limitations of our study there is another variable contributing to these difference that we were not able to identify. In two studies examining sTREM-1 and Presepsin in adult patients who received cardiopulmonary bypass for surgery, the values of sTREM-1 in our study were quite similar, while the values of Presepsin were much higher in our patients [ 13, 30 ]. We were unable to perform subgroup analysis for neonates as there was only one included in our study.
The immediate post-cannulation values of presepsin, CRP and Procalcitonin were all elevated compared to their precannulation values, while sTREM-1 was lower post-cannulation, however none of these changes reached significance. These increases in CRP and procalcitonin are consistent with previous literature and may be related to the cytokine release that occurs following cannulation [ 12, 31 ]. Some literature exists suggesting that MCS itself may impair the innate immune system, of which both sTREM-1 and presepsin are components, and may predispose patients to the development of nosocomial infections [ 12, 32 – 34 ]. While this may explain lower sTREM-1 values it does not provide a clear explanation for the elevated Presepsin values. The average CRP value was significantly greater post cannulation compared to pre cannulation suggesting that MCS itself may increase CRP, making it less useful for the detection of new infection on MCS. Comparatively, average post cannulation procalcitonin was not significantly different from pre cannulation values suggesting that procalcitonin may have utility for the detection of new infectiononMCS.
Novel biomarkers sTREM-1 and Presepsin were chosen for this analysis as prior literature has suggested that these may be more specific for new infection rather than an inflammatory response, which we believed would reduce the impact MCS would have on their behavior [ 6 ]. In our small pilot study neither sTREM-1 nor Presepsin appear to be impacted by the cannulation event with no difference between the immediate pre and post cannulation values of these two biomarkers. Additionally, neither sTREM-1 nor Presepsin appear to increase or decrease over the period of MCS support and there is no difference between pre cannulation and average post cannulation values for these two biomarkers during uninfected time periods. These data suggest that these biomarkers may be unaffected by the inflammatory response of cannulation for MCS. Our data appears to show a significant decrease in presepsin and procalcitonin in advance of the development of new infection on MCS. This was surprising as this direction of change was unexpected, with published literature describing each of these biomarkers increasing with the development of new infection [ 6, 9 ].
After cannulation it appears that there is an initial increase in CRP with subsequent stabilization and relatively unchanged levels of procalcitonin, sTREM-1 and Presepsin. The changes in CRP observed may be explained by the initial inflammatory response to the exposure to foreign substances in the form of the MCS circuit with subsequent normalization of the inflammatory levels consistent with previously published literature [ 4, 7, 11, 12 ].