Low dose Iloprost effect on platelet aggregation in comatose out-of-hospital cardiac arrest patients: A predefined sub-study of the ENDO-RCA randomized -phase 2- trial.

PURPOSE: This is a predefined sub-study of the Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA) trial. We aim to investigate Iloprost, a prostacyclin analogue, safety by evaluating change in whole blood platelet aggregometry (Multiplate) in out of hospital cardiac arrest (OHCA) patients from baseline to 96-h post randomization. METHODS: A randomized, placebo controlled double-blinded trial in 46 OHCA patients. Patients were allocated 1:2 to 48 h Iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Platelet aggregation was determined by platelet aggregation tests ASPI-test (arachidonic acid); TRAP-test (thrombin-receptor activating peptide (TRAP)-6; RISTO test (Ristocetin); ADP test (adenosin diphosphat). RESULTS: There was no significant difference between the iloprost and placebo groups according to ASPI, TRAP, RISTO and ADP platelet aggregation assays. Further, no significant differences regarding risk of bleeding were found between groups (Risk of bleeding: ASPI <40 U; TRAP <92 U; RISTO <35 U; ADP <50 U). CONCLUSIONS: In conclusion, the iloprost infusion did not influence platelet aggregation as evaluated by the ASPI, TRAP, RISTO and ADP assays. There was no increased risk of bleeding or transfusion therapy. A decline in platelet aggregation was observed for the ASPI and ADP assays during the initial 96 h after OHCA. TRIAL REGISTRATION: Trial registration at clinicaltrials.gov (identifier NCT02685618) on 18-02-2016.

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation in men.

Phenylephrine increases mean arterial pressure (MAP) by enhanced total peripheral resistance (TPR) but near-infrared spectroscopy (NIRS) determined muscle oxygenation (SmO2) increases. We addressed that apparent paradox during supine rest and head-up tilt (HUT). Variables were determined ± phenylephrine in males during supine rest (n = 17) and 40° HUT (n = 7). MAP, stroke volume (SV), heart rate (HR), and TPR were derived by Modelflow® and NIRS determined biceps SmO2 and (tibial) bone oxygenation (StibialO2). For ten subjects, cardiac filling and the diameter of the inferior caval vein (ICV collapsibility index: ((ICVexpiration - ICVinspiration)/ICVexpiration) × 100) were assessed by ultrasound. Pancreatic polypeptide (PP) and atrial natriuretic peptide (proANP) in plasma were determined by immunoassay. Brachial artery blood flow was assessed by ultrasound and skin oxygenation (SskinO2) monitored by white light spectroscopy. Phenylephrine increased MAP by 34% and TPR (62%; P < 0.001) during supine rest. The ICV collapsibility index decreased (24%; P < 0.001) indicating augmented cardiac preload although volume of the left atrium and ventricle did not change. SV increased (18%; P < 0.001) as HR decreased (24%; P < 0.001). ProANP increased by 9% (P = 0.002) with unaffected PP. Brachial artery blood flow tended to decrease while SskinO2 together with StibialO2 decreased by 11% (P = 0.026) and 20% (P < 0.001), respectively. Conversely, phenylephrine increased SmO2 (9%) and restored the HUT elicited decrease in SmO2 (by 19%) along with SV (P = 0.02). Phenylephrine reduces skin and bone oxygenation and tends to reduce arm blood flow, suggesting that the increase in SmO2 reflects veno-constriction with consequent centralization of the blood volume.