Major bleeding complications in critically ill patients with COVID-19 pneumonia.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.

Impact of fluid challenge increase in cardiac output on the relationship between systemic and cerebral hemodynamics in severe sepsis compared to brain injury and controls.

BACKGROUND: Cognitive dysfunction and delirium after ICU are frequent and may partially result from brain ischemia episodes. We hypothesized that systemic inflammation (severe sepsis or septic shock) modifies the control of brain circulation and the relation between systemic and cerebral hemodynamic after a positive response to fluid challenge (FC). METHODS: Three groups of patients were studied if they increased stroke volume (SV) > 10% after 250 or 500 ml of crystalloids: control group: patients free of comorbidity anesthetized for orthopedic surgery; sepsis group: patients with severe sepsis or septic shock (classic definition); brain injury (BI) group: trauma brain jury or hemorrhagic stroke with no detectable systemic inflammation. The measurements before and after FC were mean arterial blood pressure (MAP) (radial catheter); SV and cardiac output (CO; transesophageal Doppler); bilateral middle cerebral artery (MCAv) velocity with peak systolic (PSV) and end diastolic (EDV) values (transcranial Doppler); end-tidal CO2. The role of MAP increase was investigated by an arbitrarily threshold increase of 5%, called responder in CO and MAP (RR). The remaining patients were call responders in CO and non-responders in MAP (RnR). Nonparametric tests were used for statistical analysis. RESULTS: Among the 86 screened patients, 66 have completed the protocol: 17 in control group; 38 in sepsis group; and 11 in BI group. All patients increased SV > 10% after FC. Only the sepsis group increased MAP [+ 12 (2-25%), p < 0.05] with a significant increase in PSV and EDV [(17 (3-30)% and 17 (12-42)%, respectively (p < 0.05)], which did not change in the two other groups. The septic RR or RnR had similar variations in MCAv after FC. The baseline MAP < or > baseline median MAP had similar MCAv. CONCLUSIONS: After a FC-induced increase in SV, MCAv (PSV and EDV) increased only in septic group, mostly independently from MAP increase and from baseline MAP level. Cerebral perfusion becomes passively dependent on systemic blood flow, suggesting a modification of the control of cerebrovascular tone in sepsis-induced systemic inflammation. This information has been considered in the clinical management of septic patients.