IntroductionDanger-associated molecular patterns (DAMPs) can elicit immune responses and may subsequently induce an immune-suppressed state. Previous work showed that increased plasma levels of DAMPs are associated with immune suppression and increased susceptibility toward infections in trauma patients. Like trauma, major surgical procedures, such as cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), are also thought to cause profound DAMP release. Furthermore, the incidence of postoperative infections in these patients, ranging from 10 to 36%, is very high compared to that observed in patients undergoing other major surgical procedures. We hypothesized that the double hit of surgical trauma (CRS) in combination with HIPEC causes excessive DAMP release, which in turn contributes to the development of immune suppression. To investigate this, we assessed DAMP release in patients undergoing CRS-HIPEC, and investigated its relationship with immune suppression and postoperative infections.MethodsIn 20 patients undergoing CRS-HIPEC, blood was obtained at five time points: just before surgery (baseline), after CRS, after HIPEC, at ICU admission, and 1 day after surgery. Circulating levels of DAMPs [heat shock protein (HSP)70, high mobility group box (HMGB)1, S100A12, S100A8/S100A9, nuclear (n)DNA, mitochondrial (mt)DNA, lactate dehydrogenase (LDH), a marker of unscheduled cell death], and cytokines [tumor necrosis factor (TNF)α, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and MCP-1] were measured. The extent of immune suppression was determined by measuring HLA-DR gene expression and ex vivo leukocytic cytokine production capacity.ResultsPlasma levels of DAMPs (maximum fold increases of HSP70: 2.1 [1.5–2.8], HMGB1: 5.9 [3.2–9.8], S100A8/S100A9: 3.6 [1.8–5.6], S100A12: 2.6 [1.8–4.3], nDNA 3.9 [1.0–10.8], LDH 1.7 [1.2–2.5]), and all measured cytokines increased profoundly following CRS-HIPEC. Evidence of immune suppression was already apparent during the procedure, illustrated by a decrease of HLA-DR expression compared with baseline (0.5-fold [0.3–0.9]) and diminished ex vivo pro-inflammatory cytokine production capacity. The increase in HMGB1 levels correlated with the decrease in HLA-DR expression (r = −0.46, p = 0.04), and peak HMGB1 concentrations were significantly higher in the five patients who went on to develop a postoperative infection (p = 0.04).ConclusionCRS-HIPEC is associated with profound DAMP release and immune suppression, and plasma HMGB1 levels are related with the occurrence of postoperative infections in these patients.

BackgroundCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are high-risk extensive abdominal surgery. During high-risk surgery, less invasive methods for cardiac index (CI) measurement have been widely used in operating theater. We investigated the accuracy of CI derived from different methods (FroTrac, ProAQT, ClearSight, and arterial pressure waveform analysis [APWA], from PICCO) and compared them to transpulmonary thermodilution (TPTD) during CRS and HIPEC in the operative room and intensive care unit (ICU).MethodsTwenty-five patients scheduled for CRS-HIPEC were enrolled. During nine predefined time-points, simultaneous hemodynamic measurements were performed in the operating room and ICU. Absolute and relative changes of CI were analyzed using a Bland-Altman plot, four-quadrant plot, and interchangeability.ResultsThe mean bias was −0.1 L/min/m2 for ClearSight, ProAQT, and APWA and was −0.2 L/min/m2 for FloTrac compared with TPTD. All devices had large limits of agreement (LoA). The percentage of errors and interchangeabilities for ClearSight, FloTrac, ProAQT, and APWA were 50%, 50%, 54%, 36% and 36%, 47%, 40%, 72%, respectively. Trending capabilities expressed as concordance using clinically significant CI changes were −7º ± 39º, −19º ± 38º, −13º ± 41º, and −15º ± 39º. Interchangeability in trending showed low percentages of interchangeable and gray zone data pairs for all devices.ConclusionsDuring CRS-HIPEC, ClearSight, FloTrac and ProAQT systems were not able to reliably measure CI compared to TPTD. Reproducibility of changes over time using concordance, angular bias, radial LoA, and interchangeability in trending of all devices was unsatisfactory.

BACKGROUND In most Dutch hospitals, because of putative peri-operative swelling of the fingers, patients must remove rings before entering the operating theatre. If this proves impossible, destructive methods for removal may be required. For some patients, this might be too radical, as the risk of wearing rings may not be in proportion to the economic and emotional damage to the patient. OBJECTIVE The objective of this study was to determine whether peri-operative swelling of fingers occurs in elective surgery patients. DESIGN A prospective observational study. SETTING University Medical Centre. PATIENTS Five groups of patients: major cardiothoracic surgery, major noncardiothoracic surgery, nonmajor surgery with a minimum of one overnight stay, nonmajor surgery without overnight stay and surgery under intrathecal anaesthesia. MAIN OUTCOME MEASURE Finger swelling, as measured by the circumference of the first phalanx of the middle and ring fingers of both hands, pre-operatively and at 3, 24 and 48 h postsurgery, using a roller tape with one winding and 20-g weights in a custom-made frame. RESULTS One hundred and forty-eight patients were enrolled. Peri-operative swelling reached statistical significance in all groups and was most prominent in major cardiothoracic and noncardiothoracic surgery (maximum increases in circumference were 10.6 and 7.3%, respectively). In all groups, maximal swelling was observed 24 h postsurgery. CONCLUSION Peri-operative swelling of fingers is a common phenomenon, which is related to the extent of the surgical procedure. TRIAL REGISTRATION Netherlands Trial Register NL8066.

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