Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial).

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg-1 based on factor IX) or fresh frozen plasma (15 ml.kg-1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

Ambient temperature and activation of implantable cardioverter defibrillators.

The degree to which weather influences the occurrence of serious cardiac arrhythmias is not fully understood. To investigate, we studied the timing of activation of implanted cardiac defibrillators (ICDs) in relation to daily outdoor temperatures using a fixed stratum case-crossover approach. All patients attending ICD clinics in London between 1995 and 2003 were recruited onto the study. Temperature exposure for each ICD patient was determined by linking each patient's postcode of residence to their nearest temperature monitoring station in London and the South of England. There were 5,038 activations during the study period. Graphical inspection of ICD activation against temperature suggested increased risk at lower but not higher temperatures. For every 1 °C decrease in ambient temperature, risk of ventricular arrhythmias up to 7 days later increased by 1.2 % (95 % CI -0.6 %, 2.9 %). In threshold models, risk of ventricular arrhythmias increased by 11.2 % (0.5 %, 23.1 %) for every 1° decrease in temperature below 2 °C. Patients over the age of 65 exhibited the highest risk. This large study suggests an inverse relationship between ambient outdoor temperature and risk of ventricular arrhythmias. The highest risk was found for patients over the age of 65. This provides evidence about a mechanism for some cases of low-temperature cardiac death, and suggests a possible strategy for reducing risk among selected cardiac patients by encouraging behaviour modification to minimise cold exposure.