Association of hyperfibrinolysis with poor prognosis in refractory circulatory arrest: implications for extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR. We explored early detection of hyperfibrinolysis in patients with refractory OHCA referred for eCPR. METHODS: We analysed ROTEM results and resuscitation parameters of 57 adult patients with ongoing OHCA who presented to our ICU for eCPR evaluation. RESULTS: Hyperfibrinolysis, defined as maximum lysis ≥15%, was present in 36 patients (63%) and was associated with higher serum lactate, lower arterial blood pH, and increased low-flow intervals. Of 42 patients who achieved return of circulation, 28 had a poor 30-day outcome. The incidence of hyperfibrinolysis was higher in the poor outcome group compared with patients with good outcomes (75% [21 of 28] vs 7.1% [1 of 14]; P<0.001). The ratio of EXTEM A5 to lactate concentration showed good predictive value in detecting hyperfibrinolysis (AUC of 0.89 [95% confidence interval 0.8-1]). CONCLUSIONS: Hyperfibrinolysis was common in patients with refractory cardiac arrest, and was associated with poor prognosis. The combination of high lactate with early clot firmness values, such as EXTEM A5, appears promising for early detection of hyperfibrinolysis. This finding could facilitate decisions to perform eCPR, particularly for patients with prolonged low-flow duration but lacking hyperfibrinolysis.

Hemodialysis and biotransformation of erythrocyte epoxy fatty acids in peripheral tissue.

Cardiovascular disease is the leading cause of mortality in patients with renal failure. Red blood cells (RBCs) are potential reservoirs for epoxy fatty acids (oxylipins) that regulate cardiovascular function. Hemoglobin exhibits pseudo-lipoxygenase activity in vitro. We previously assessed the impact of single hemodialysis (HD) treatment on RBC epoxy fatty acids status in circulating arterial blood and found that eicosanoids in oxygenated RBCs could be particularly vulnerable in chronic kidney disease and hemodialysis. The purpose of the present study was to evaluate the differences of RBC epoxy fatty acids profiles in arterial and venous blood in vivo (AV differences) from patients treated by HD treatment. We collected arterial and venous blood samples in upper limbs from 12 end-stage renal disease (ESRD) patients (age 72±12 years) before and after HD treatment. We measured oxylipins derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways in RBCs by LC-MS/MS tandem mass spectrometry. Our data demonstrate arteriovenous differences in LOX pathway metabolites in RBCs after dialysis, including numerous hydroxyeicosatetraenoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and hydroxyeicosapentaenoic acids (HEPEs). We detected more pronounced changes in free metabolites in RBCs after HD, as compared with the total RBC compartment. Hemodialysis treatment did not affect the majority of CYP and CYP ω/(ω-1)-hydroxylase products in RBCs. Our data indicate that erythro-metabolites of the LOX pathway are influenced by renal-replacement therapies, which could have deleterious effects in the circulation.

Hemodialysis and Plasma Oxylipin Biotransformation in Peripheral Tissue.

Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.