Impact of Additional Administration of von Willebrand Factor Concentrates to Thrombocyte Transfusion in Perioperative Bleeding in Cardiac Surgery.

Background: Von Willebrand factor (vWF) is an important part of blood coagulation since it binds platelets to each other and to endothelial cells. In traumatic and surgical haemorrhage, both blood cells and plasmatic factors are consumed, leading to consumption coagulopathy and fluid resuscitation. This often results in large amounts of crystalloids and blood products being infused. Additional administration of vWF complex and platelets might mitigate this problem. We hypothesize that administration of vWF concentrate additionally to platelet concentrates reduces blood loss and the amount of blood products (platelets, red blood cells [RBC], fresh frozen plasma [FFP]) administered. Methods: We conducted a monocentric 6-year retrospective data analysis of cardiac surgery patients. Included were all patients receiving platelet concentrates within 48 h postoperatively. Patients who additionally received vWF concentrates were allocated to the intervention group and all others to the control group. Groups were compared in mixed regression models correcting for known confounders, based on nearest neighbour propensity score matching. Primary endpoints were loss of blood (day one and two) and amount of needed blood products on day one and two (platelets, RBC, FFP). Secondary endpoints were intensive care unit (ICU) and in-hospital length of stay, ICU and in-hospital mortality, and absolute difference of platelet counts before and after treatment. Results: Of 497 patients analysed, 168 (34%) received vWF concentrates. 121 patients in both groups were considered for nearest neighbour matching. Patients receiving additional vWF were more likely to receive more blood products (RBC, FFP, platelets) in the first 24 h after surgery and had around 200 mL more blood loss at the same time. Conclusion: In this retrospective analysis, no benefit in additional administration of vWF to platelet concentrates on perioperative blood loss, transfusion requirement (platelets, RBC, FFP), length of stay, and mortality could be found. These findings should be verified in a prospective randomized controlled clinical trial (www.clinicaltrials.gov identifier NCT04555785).

A new high protein-to-energy enteral formula with a whey protein hydrolysate to achieve protein targets in critically ill patients: a prospective observational tolerability study.

OBJECTIVES: Current guidelines and expert recommendations stress the need to implement enteral feeds with a higher protein-to-energy ratio to meet protein requirements as recommended while avoiding gastrointestinal side effects and energy overfeeding in ICU patients. MATERIALS AND METHODS: Prospective tolerability study in 18 critically ill patients with a high protein formula (high protein-to-energy (HP:E) formula = Fresubin® Intensive; HPG) compared to a contemporary matched conventional therapy group (CTG). The primary outcome was GI intolerance defined as ≥300 ml daily gastric residual volume (GRV), vomiting, or diarrhea on days 1 and 2. Secondary outcomes were the percentage of patients reaching their protein target on day 4 and overall protein intake. RESULTS: Groups were comparable regarding demographic characteristics, disease severity, organ failures, mechanical ventilation, and NUTRIC score at baseline. Eighteen patients completed the 4-day feeding period. The number of events of GRV of ≥300 ml/day was equal in both groups (33.3%). The incidence of diarrhea and vomiting was low in the HPG (two patients concerned). EN did not need to be discontinued due to intolerance in any group. Seventy-two percent of patients reached protein targets ≥1.3 g/kgBW/d within 4 days after initiation of enteral feeding, which was superior to the CTG (33%). Post-hoc testing showed group differences of protein intake between HPG and CTG were significant at t = 72 h and t = 96 h. Energy targets were met in both groups. CONCLUSION: The HP:E formula containing 33% whey protein hydrolysate is well tolerated in this tolerability study. Due to the HP:E ratio protein targets can be reached faster. Larger randomized trials are needed to confirm preliminary results. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02678325. Registered 2 May 2016.

Comparison of propofol and dexmedetomidine infused overnight to treat hyperactive and mixed ICU delirium: a protocol for the Basel ProDex clinical trial.

BACKGROUND/OBJECTIVES: Delirium is a neurobehavioural disturbance that frequently develops particularly in the intensive care unit (ICU) population. It was first described more than half a century ago, where it was already discovered as a state that might come along with serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. However, in most cases, there is still lack of proof for causal relationship. Its presence frequently remains unrecognised due to suggested predominance of the hypoactive form. Furthermore, in the general ICU population, it has been shown that the duration of delirium is associated with worse long-term cognitive function. Due to the multifactorial origin of delirium, we have several but no incontestable treatment options. Nonetheless, delirium bears a high burden for patient, family members and the medical care team.The Basel ProDex Study targets improvement of hyperactive and mixed delirium therapy in critically ill patients. We will focus on reducing the duration and severity of delirium by implementing dexmedetomidine into the treatment plan. Dexmedetomidine compared with other sedatives shows fewer side effects representing a better risk profile for delirium treatment in general. This could further contribute to higher patient safety.The aim of the BaProDex Trial is to assess the superiority of dexmedetomidine to propofol for treatment of hyperactive and mixed delirium in the ICU. We hypothesise that dexmedetomidine, compared with propofol administered at night, shortens both the duration and severity of delirium. METHODS/DESIGN: The Basel ProDex Study is an investigator-initiated, one-institutional, two-centre randomised controlled clinical trial for the treatment of delirium with dexmedetomidine versus propofol in 316 critically ill patients suffering from hyperactive and mixed delirium. The primary outcome measure is delirium duration in hours. Secondary outcomes include delirium-free days at day 28, death at day 28, delirium severity, amount of ventilator days, amount of rescue sedation with haloperidol, length of ICU and hospital stay, and pharmaceutical economic analysis of the treatments. Sample size was estimated to be able to show the superiority of dexmedetomidine compared with propofol regarding the duration of delirium in hours. The trial will be externally monitored according to good clinical practice (GCP) requirements. There are no interim analyses planned for this trial. ETHICS AND DISSEMINATION: This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonization- Good Clinical Practice (ICH-GCP) or Europäische Norm International Organization for Standardization (ISO EN 14155; as far as applicable) as well as all national legal and regulatory requirements. Only the study team will have access to trial specific data. Anonymisation will be achieved by a unique patient identification code. Trial data will be archived for a minimum of 10 years after study termination. We plan to publish the data in a major peer-reviewed clinical journal. TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT02807467 PROTOCOL VERSION: Clinical Study Protocol Version 2, 16.08.2016.