Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis Gambro-Hospal, Meyzieu, FranceHeparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standardof-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standardof-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.

BackgroundAnticoagulation for chronic dialysis patients with contraindications to heparin administration is challenging. Current guidelines state that in patients with increased bleeding risks, strategies that can induce systemic anticoagulation should be avoided. Heparin-free dialysis using intermittent saline flushes is widely adopted as the method of choice for patients at risk of bleeding, although on-line blood predilution may also be used. A new dialyzer, Evodial (Gambro, Lund, Sweden), is grafted with unfractionated heparin during the manufacturing process and may allow safe and efficient heparin-free hemodialysis sessions. In the present trial, Evodial was compared to standard care with either saline flushes or blood predilution.MethodsThe HepZero study is the first international (seven countries), multicenter (10 centers), randomized, controlled, open-label, non-inferiority (and if applicable subsequently, superiority) trial with two parallel groups, comprising 252 end-stage renal disease patients treated by maintenance hemodialysis for at least 3 months and requiring heparin-free dialysis treatments. Patients will be treated during a maximum of three heparin-free dialysis treatments with either saline flushes or blood predilution (control group), or Evodial. The first heparin-free dialysis treatment will be considered successful when there is: no complete occlusion of air traps or dialyzer rendering dialysis impossible; no additional saline flushes to prevent clotting; no change of dialyzer or blood lines because of clotting; and no premature termination (early rinse-back) because of clotting.The primary objectives of the study are to determine the effectiveness of the Evodial dialyzer, compared with standard care in terms of successful treatments during the first heparin-free dialysis. If the non-inferiority of Evodial is demonstrated then the superiority of Evodial over standard care will be tested. The HepZero study results may have major clinical implications for patient care.Trial registrationClinicalTrials.gov NCT01318486

reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. carbon dioxide 30 [27][28][29][30][31][32][33][34][35] mmHg and median temperature 37.1 [36.8-37.3]°C. After removal of artefacts, the mean monitoring time was 22 h08 (8 h54). All patients had impaired cerebral autoregulation during their monitoring time. The mean IAR index was 17 (9.5) %. During H 0 H 6 and H 18 H 24 , the majority of our patients; respectively 53 and 71 % had an IAR index > 10 %. Conclusion According to our data, patients with septic shock had impaired cerebral autoregulation within the first 24 hours of their admission in the ICU. In our patients, we described a variability of distribution of impaired autoregulation according to time. ReferencesSchramm P, Klein KU, Falkenberg L, et al. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care 2012; 16: R181. Aries MJH, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit. Care Med. 2012.

Introduction and Aims: The Frequent Hemodialysis Network Nocturnal trial randomized 87 subjects to 6 times per week home nocturnal hemodialysis (FNHD) or to 3 times per week hemodialysis (3HD) for 1 year. Subjects were subsequently free to modify their treatment schedule. We describe effects of randomized treatment assignment on mortality over a median follow-up of 3.7 years. Methods: We obtained dates of death and kidney transplantation through July 2011 using linkage to USRDS and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment. Results: For randomized subjects (FNHD vs. 3HD), 62% vs. 0%, 51% vs. 27%, and 52% vs. 33% received frequent long hemodialysis (≥27 hours of dialysis over ≥4.5 treatments per week) during the trial, the first year after the trial, and subsequently. There were 14 deaths in the FNHD arm and 5 deaths in the 3HD arm overall; during the first year after the trial there were 9 deaths in the FNHD arm and 1 death in the 3HD arm. The overall mortality hazard ratio for randomization to FNHD vs. 3HD was 3.88, (95% CI: 1.27 to 11.79), p = 0.01. The 19 deaths in the two treatment groups included 9 deaths related to cardiac causes, 2 to infection, and 1 to the dialysis procedure itself (unrecognized central venous catheter disconnection at night in a subject randomized to FNHD). Three deaths, all in the conventional group, were due to cancer. The finding of higher mortality for patients randomized to FNHD compared to 3HD was observed consistently for all-cause mortality over the entire follow-up (14 vs. 5 deaths), all-cause mortality censoring transplants (14 deaths vs. 4 deaths), cardiac or infectious deaths (9 vs. 2 deaths), and deaths of all causes excluding cancer (14 vs. 2 deaths).Pre-specified subgroups were tested for interaction with mortality, including age, sex, race, Canadian vs. U.S. center, experienced vs. inexperienced center, ESRD vintage, or baseline left ventricular mass; none approached statistical significance. The trend toward higher mortality in the FNHD group was particularly marked among patients with ≤ 500 ml/day of urine volume at baseline. Vascular access events did not appear to predict mortality: in the FNHD group, 12 post-trial deaths in 43 subjects were evenly distributed among those with and those without vascular access events during the randomized trial phase.The results of as-treated analyses relating mortality to a patient's exposure to frequent long hemodialysis (≥27 hours/week and ≥4.5 treatments/week) over the previous 12 months was 3.06 (95% CI 1.11 to 8.43, p = 0.03) and over the previous 6 months was 1.12 (95% CI: 0.44 to 3.22, p = 0.74). The attenuation of the as-treated hazard ratio reflected the reclassification of 3 deaths from the frequent long category using the 12 month running average to the non-frequent long category using the six month moving average. Conclusions: Our observation of higher mortality among subjects randomized to FNHD compared to 3HD raises concerns regard...