Comparative before-after study of fever prevention versus targeted temperature management following out-of-hospital cardiac arrest.

Background: International guidelines for neuroprotection following out-of-hospital cardiac arrest (OHCA) recommend fever prevention ahead of routine temperature management. This study aimed to identify any effect of changing from targeted temperature management to fever prevention on neurological outcome following OHCA. Methods: A retrospective observational cohort study was conducted of consecutive admissions to an ICU at a tertiary OHCA centre. Comparison was made between a period of protocolised targeted temperature management (TTM) to 36 °C and a period of fever prevention. Results: Data were available for 183 patients. Active temperature management was administered in 86/118 (72%) of the TTM cohort and 20/65 (31%) of the fever prevention group. The median highest temperature prior to the start of temperature management was significantly lower in the TTM group at 35.6 (IQR 34.9-36.2) compared to 37.9 °C (IQR 37.7-38.2) in the fever prevention group (adjusted p < 0.001).There was no difference in the proportion of patients discharged with Cerebral Performance Category 1 or 2 between the groups (42% vs. 40%, p = 0.88). Patients in the fever prevention group required a reduced duration of noradrenaline (36 vs. 46 h, p = 0.03) and a trend towards a reduced duration of propofol (37 vs. 56 h, p = 0.06).In unadjusted analysis, use of active temperature management (irrespective of group) appeared to be associated with decreased risk of poor outcome (OR = 0.43, 95% CI 0.23-0.78) but after adjustment for patient age, presenting rhythm, witnessed arrest and duration of CPR, this was no longer significant (OR = 0.93, 95% CI 0.37-2.31, p = 0.88). Conclusion: Switching from TTM to fever prevention following OHCA was associated with similar rates of neurological outcomes, with a possible decrease in sedation and vasopressor requirements.

Aspirin has little additional anti-platelet effect in healthy volunteers receiving prasugrel.

BACKGROUND: Strong P2Y(12) blockade, as can be achieved with novel anti-platelet agents such as prasugrel, has been shown in vitro to inhibit both ADP and thromboxane A(2) -mediated pathways of platelet aggregation, calling into question the need for the concomitant use of aspirin. OBJECTIVE: The present study investigated the hypothesis that aspirin provides little additional anti-aggregatory effect in a group of healthy volunteers taking prasugrel. STUDY PARTICIPANTS/METHODS: In all, 9 males, aged 18 to 40 years, enrolled into the 21-day study. Prasugrel was loaded at 60 mg on day 1 and maintained at 10 mg until day 21. At day 8, aspirin 75 mg was introduced and the dose increased to 300 mg on day 15. On days 0, 7, 14 and 21, platelet function was assessed by aggregometry, response to treatments was determined by VerifyNow and urine samples were collected for quantification of prostanoid metabolites. RESULTS: At day 7, aggregation responses to a range of platelet agonists were reduced and there was only a small further inhibition of aggregation to TRAP-6, collagen and epinephrine at days 14 and 21, when aspirin was included with prasugrel. Urinary prostanoid metabolites were unaffected by prasugrel, and were reduced by the addition of aspirin, independent of dose. CONCLUSIONS: In healthy volunteers, prasugrel produces a strong anti-aggregatory effect, which is little enhanced by the addition of aspirin. The addition of aspirin as a dual-therapy with potent P2Y(12) receptor inhibitors warrants further investigation.

In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation.

BACKGROUND: Aspirin and antagonists of platelet ADP P2Y(12) receptors are often coprescribed for protection against thrombotic events. However, blockade of platelet P2Y(12) receptors can inhibit thromboxane A(2) (TXA(2))-dependent pathways of platelet activation independently of aspirin. OBJECTIVES: To assess in vitro whether aspirin adds additional antiaggregatory effects to strong P2Y(12) receptor blockade. METHODS: With the use of platelet-rich plasma from healthy volunteers, determinations were made in 96-well plates of platelet aggregation, TXA(2) production and ADP/ATP release caused by ADP, arachidonic acid, collagen, epinephrine, TRAP-6 amide and U46619 (six concentrations of each) in the presence of prasugrel active metabolite (PAM; 0.1-10 µmol L(-1)), aspirin (30 µmol L(-1)), PAM + aspirin or vehicle. results: PAM concentration-dependently inhibited aggregation; for example, aggregation in response to all concentrations of ADP and U46619 was inhibited by ≥ 95% by PAM at > 3 µmol L(-1) . In further tests of PAM (3 µmol L(-1)), aspirin (30 µmol L(-1)) and PAM + aspirin, aspirin generally failed to produce more inhibition than PAM or additional inhibition to that caused by PAM. The antiaggregatory effects of PAM were associated with reductions in the platelet release of both TXA(2) and ATP + ADP. Similar effects were found when either citrate or lepirudin were used as anticoagulants, and when traditional light transmission aggregometry was conducted at low stirring speeds. CONCLUSIONS: P2Y(12) receptors are critical to the generation of irreversible aggregation through the TXA(2) -dependent pathway. As a result, strong P2Y(12) receptor blockade alone causes inhibition of platelet aggregation that is little enhanced by aspirin. The clinical relevance of these observations remains to be determined.