Niels Erikstrup Clausen

The socioeconomic burden of excessive alcohol consumption is high worldwide [1], and treatment of alcohol withdrawal symptoms is one of the most frequent causes of admissions to an intensive care u...

Background: Septic shock is associated with high morbidity and mortality, the endothelium plays an important role. Crystalloids is standard of care to maintain intravascular volume. Plasma is associated with improved endothelial integrity and restoration of the glycocalyx layer. We evaluated the efficacy and safety aspects of cell‐free and pathogen inactivated pooled plasma (OctaplasLG®) as resuscitation in septic shock patients.Study Design and Methods: This randomized, investigator‐initiated phase IIa trial ran at a Danish single center intensive care unit, from 2017 to 2019. Patients were 18 years of age or older with septic shock and randomized to fluid optimization with OctaplasLG® or Ringer‐acetate in the first 24 h. The primary endpoints were changes in biomarkers indicative of endothelial activation, damage, and microvascular perfusion from baseline to 24 h. Safety events and mortality were assessed during 90 days.Results: Forty‐four patients were randomized, 20 to OctaplasLG versus 24 to Ringer‐acetate. The median age was 69, and 55% were men. Median Sequential Organ Failure Assessment score was 13. Baseline differences favoring the Ringer‐acetate group were observed. The OctaplasLG® group was resuscitated with 740 mL plasma and the Ringer‐acetate group with 841 mL crystalloids. There was no significant change in the microvascular perfusion or five biomarkers except VEGFR1 change, which was higher in patients receiving OctaplasLG® 0.12(SD 0.37) versus Ringer‐acetate −0.24 (SD 0.39), with mean difference 0.36 (95% CI, 0.13–0.59, p = .003) in favor of Ringer‐acetate.Discussion: This study found that fluid resuscitation with OctaplasLG® in critically ill septic shock patients is feasible. Baseline confounding prevented assessment of the potential effect of OctaplasLG®.

Background: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. Study design and methods: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 x 10(9)/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. Results: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 x 10(11) platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 x 10(11) platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) x 10(9)/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. Conclusions: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

Purpose Thrombocytopenia (platelet count < 150 × 10⁹/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Objectives: To investigate the effect of continuous infusion of the potential endothelial cytoprotective agent prostacyclin (Iloprost) 1 ng/kg/min vs. placebo for 72 hours on pulmonary endotheliopathy in mechanically ventilated COVID-19 patients. Trial design: A multicenter, randomized (1:1, active: placebo), blinded, parallel group exploratory trial Participants: Inclusion criteria are: Adult patients (>18 years); Confirmed COVID-19 infection; Need for mechanical interventions; Endothelial biomarker soluble thrombomodulin >4ng/ml. Exclusion criteria: Withdrawal from active therapy; Pregnancy (non-pregnancy confirmed by patient being postmenopausal (age 60 or above) or having a negative urine- or plasma-hCG); Known hypersensitivity to iloprost or to any of the other ingredients; Previously included in this trial or a prostacyclin trial within 30 days; Consent cannot be obtained; Life-threatening bleeding defined by the treating physician; Known severe heart failure (NYHA class IV); Suspected acute coronary syndrome The study is conducted at five intensive care units in the Capital Region of Denmark at Rigshospitalet, Herlev Hospital, Hvidovre Hospital, Bispebjerg Hospital, Nordsjællands Hospital. Intervention and comparator: The patients are randomized to 72-hours continuous infusion of either prostacyclin (Iloprost/Ilomedin) at a dose of 1 ng/kg/min or Placebo (normal saline). Main outcomes: Primary endpoint: Days alive without mechanical ventilation in the intensive care units within 28 days Randomisation: The randomisation sequence is performed in permuted blocks of variable sizes stratified for trial site using centralised, concealed allocation. The randomisation sequence is generated 1:1 (active/placebo) using the online randomisation software ‘Sealed Envelope’ (https://www.sealedenvelope.com/). Once generated the randomisation sequence is formatted and uploaded into Research Electronic Data Capture system (REDCap) to facilitate centralised, web-based allocation according to local written instruction. Blinding (masking): The following are blinded: all clinicians, patients, investigators, and those assessing the outcomes including the statisticians. Numbers to be randomised (sample size): Forty patients are planned to be randomized to each group, with a total sample size of 80 patients. Trial Status: Protocol version 1.4 dated May 25, 2020. Recruitment is ongoing. The recruitment was started June 15, 2020 and the anticipated finish of recruitment is February 28, 2021 with 90 days follow up hereafter. Trial registration: Trial registration at clinicaltrialregisters.eu; EudraCT no. 2020-001296-33 on 3 April 2020 and at ClinicalTrials.gov Identifier: NCT04420741 on 9 June 2020 Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

This anthropological study explores children's non-social reactions during the active treatment period, the on-treatment, in a paediatric oncology ward in a Danish university hospital. It is argued that, although some children's non-social reactions is a tactical disengagement to manage the on-treatment situation, such non-social tactics might ultimately prove an undesirable strategy with negative long-term social consequences for social survivorship. Data were generated over 7 months of ethnographic fieldwork between May 2011 and January 2013, using qualitative methods such as participant observation and open-ended interviewing. Fifty children of both sexes between 4 and 15 years, their families and hospital staff participated in the study. These data formed the basis for the study. The findings show that children's response to care challenges, including exhaustion from care management, exposure from being in a public space, and the open-ended duration of treatment, configure in tactic forms that we term social disengagement. It is suggested that such tactical social disengagement might expand into long-term social patterns, and, as such, change from an alleviating tactic to a socially isolating and damaging tactic for survivors of cancer in childhood.

Summary: Recurrent bleeding into joints initiates a sequence of events leading to a progressive joint damage in people with severe haemophilia. This is a continuous process during childhood and adolescence, therefore joint abnormalities may be minimal on physical examination in very young children – even those receiving on‐demand treatment. The aim of our study was to quantify the burden of arthropathy in Lithuanian patients who had been treated exclusively by on‐demand substitution and compare their physical joint health with age‐matched Danish patients who received prophylaxis from an early age. Boys, aged 4–17 years, with severe haemophilia and no signs of inhibitors were included in the study. Joint outcome based on the Haemophilia Joint Health Score (HJHS) was analysed in two different treatment groups and compared within the matched pairs. In total, 32 (16 in each treatment group) patients were enroled. A total of 192 joints were evaluated. Joint status according to treatment strategy was strikingly different: 27.4 for on‐demand vs. 3.3 for prophylaxis (P = 0.0002) and 3.9 vs. 36.3 (P < 0.0001) respectively. The results further demonstrate the unequivocal effect of prophylaxis on joint status and give an insight into early and late manifestations of joint impairment based on the HJHS in haemophilia patients with treatment on‐demand compared with joint changes that may develop over the time with the preventative treatment.