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.

Standard vs. carbone dioxide adapted kidney replacement therapy in hypercapnic ARDS patients: a randomized controlled pilot trial (BigBIC).

BACKGROUND: Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT. METHODS: We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO2-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment. RESULTS: From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO2-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26). CONCLUSION: Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS. TRIAL REGISTRATION: The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.

Viscoelastic testing reveals normalization of the coagulation profile 12 weeks after severe COVID-19.

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis.

BACKGROUND: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. METHODS: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. RESULTS: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. CONCLUSIONS: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.