Phosphodiesterase III inhibitors (VIVUS)

Fat embolism syndrome (FES) occurs when fat droplets from bone marrow or adipose tissue enter the circulation due to bone fractures or surgical interventions. It typically develops 12 to 72 hours after injury. However, fulminant FES, characterized by its rapid onset, is rare and can rapidly progress to a life-threatening condition. In this case report, a 90-year-old woman underwent osteosynthesis on the fourth day after admission (day 4) following a femoral diaphyseal fracture. During the insertion of an intramedullary nail into the femur, rapid deterioration of oxygenation was observed, followed by shock and severe right heart failure. Emergency veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated. Suspecting thromboembolism, contrast-enhanced CT was performed, but no massive thrombus was found in the pulmonary artery. Based on the clinical course, we diagnosed fulminant FES. The patient received respiratory and circulatory support with VA-ECMO, along with reduction of the right heart afterload using inhaled nitric oxide (iNO) and phosphodiesterase III inhibitors. The patient was successfully weaned off ECMO on day 7, iNO was discontinued on day 10, and the ventilator was removed on day 11. The patient was subsequently transferred to the general ward on day 13, where she exhibited no significant neurological deficits. Although fat embolism syndrome can only be managed symptomatically, the patient's outcome was favorable because of the prompt initiation of ECMO in response to the fulminant presentation.

We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations.

Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database. For each patient, the area between the actual lactate concentrations and 2.2 mmol/L (AUC_lact2.2), was calculated for three days.

Data on 229 patients from 10 hospitals were collected, of whom 123 received PDE3i (54%). First, a linear multivariate model was developed to predict AUC_lact2.2 (R² = 0.57). Adding PDE3i as a cofactor did not affect R². Second, 60 patients receiving PDE3i at any time between days 0 and 2 were compared to 60 propensity matched no-PDE3i patients. Third, 30 patients who received PDE3i from ICU admission to day 3 were compared to 30 propensity-matched no-PDE3i patients. These analyses showed no differences in AUC_lact2.2, SOFA scores, ICU or hospital LOS or hospital mortality between treatment groups.

No association was found between the administration of PDE3i and lactate kinetics, resolution of organ failure, ICU or hospital LOS or hospital mortality.