Pragmatic study of a thromboprophylaxis algorithm in critically ill patients with SARS-COV-2 infection.

The optimal thromboprophylactic strategy for patients affected by Coronavirus disease 2019 (COVID-19) has been debated among experts. This study evaluated the safety and efficacy of a thromboprophylaxis algorithm. This was a retrospective, single-center study in critically ill patients admitted to the intensive care unit (University affiliated Hospital) for acute respiratory failure due to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). From March 16 to April 9, 2020, thromboprophylaxis was adjusted according to weight (control group, n = 19) and after this date, thromboprophylaxis depended on an algorithm based on thrombotic and hemorrhagic risk factors (protocol group, n = 13). With regard to safety (number of major bleeding events and blood transfusions), the groups were not significantly different. With regard to efficacy, the number of thrombotic events decreased from 37 to 0%, p = 0.025 after implementation of the algorithm. Also, peak fibrinogen dropped from 8.6 (7.2-9.3) to 6.5 (4.6-8.4) g/L, p = 0.041 and D-dimers from 2194 (1464-3763) to 1486 (900-2582) ng/mL, p = 0.0001. In addition, length of stay declined from 19 (10-31) to 5 (3-19) days, p = 0.009. In conclusion, a tailored thromboprophylaxis algorithm (risk stratification based on clinical parameters and biological markers) reduce thrombotic phenomena in critically ill COVID-19 patients without increasing major bleeding.

Impact of COVID-19 on nursing time in intensive care units in Belgium.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on nursing practice in intensive care unit and consequently, on workload. OBJECTIVE: To assess the nurse-patient ratio required by COVID-19 patients and to identify the factors that influence nursing in this context. DESIGN: This study was a retrospective observational study that evaluated the ratio using the Nursing Activities Score (NAS). SETTING: Three Belgian French-speaking hospitals, including five ICUs. Patients included COVID-19 and non-COVID-19 patients. MEASUREMENTS AND MAIN RESULTS: The study included 95 COVID-19 patients and 1604 non-COVID-19 patients (control group) resulting in 905 and 5453 NAS measures, respectively. The NAS was significantly higher among the COVID-19 patients than in the control group (p = <0.0001). In the COVID-19 group, these higher scores were also observed per shift and uniformly across the three hospitals. COVID-19 patients required more time in the activities of monitoring and titration (χ2 = 457.60, p = <0.0001), mobilisation (χ2 = 161.21, p = <0.0001), and hygiene (χ2 = 557.77, p = <0.0001). Factors influencing nursing time measured by NAS in the COVID-19 patients were age <65 years old (p = 0.23), the use of continuous venovenous hemofiltration (p = 0.002), a high APACHE II score (p = 0.006) and patient death (p = 0.002). A COVID-19 diagnosis was independently associated with an increase in nursing time (OR = 4.8, 95% CI:3.6-6.4). CONCLUSIONS: Patients hospitalised in the ICU due to COVID-19 require significantly more nursing time and need an average ratio of almost 1:1.

High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial.

PURPOSE: Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI. METHODS: This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period. RESULTS: Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups. CONCLUSIONS: In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.

Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension.

Experimental left-to-right shunt-induced pulmonary arterial hypertension (PAH) can be partially prevented by the endothelin-A receptor blocker sitaxsentan or by the phosphodiesterase-5 inhibitor sildenafil. We hypothesized that the combined administration of these drugs would completely prevent shunt-induced PAH, arguing in favor of a major role of endothelial dysfunction in the initiation of the disease. Twenty-four 3-wk-old piglets were randomized to a sham operation or to placebo, sitaxsentan therapy, or sitaxsentan combined with sildenafil after the anastomosis of the left subclavian artery to the pulmonary arterial trunk. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry and quantitative real-time PCR for endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor (BMPR) signaling molecules. Three months of left-to-right shunting induced an increase in pulmonary vascular resistance (PVR) and medial thickness, an overexpression of endothelin-1, and angiopoietin-1 and decreased expressions of BMPR-2 and BMPR-1A. Sitaxsentan partially prevented a shunt-induced increase in PVR, medial thickness, and associated biological disturbances. Sildenafil combined with sitaxsentan normalized PVR, medial thickness, and the expression of endothelin-1. However, the expression of angiopoietin-1 remained increased, and the expressions of BMPR-1A and BMPR-2 were incompletely returned to normal. The coupling of right ventricular end-systolic to arterial elastances was maintained in all circumstances. Sitaxsentan combined with sildenafil prevents shunt-induced PAH more effectively than sitaxsentan alone, suggesting a major role for the targeted signaling pathways in the initiation of the disease. Sitaxsentan alone or combined with sildenafil did not affect right ventricular function.