Heparin for Moderately Ill Patients with Covid-19

Background Heparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. Methods We randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. Results At 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85). Conclusions In moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days.

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Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial

BMJ ◽

10.1136/bmj.n2400 ◽

2021 ◽

pp. n2400

Author(s):

Michelle Sholzberg ◽

Grace H Tang ◽

Hassan Rahhal ◽

Musaad AlHamzah ◽

Lisa Baumann Kreuziger ◽

...

Keyword(s):

Clinical Trial ◽

Mechanical Ventilation ◽

Major Bleeding ◽

Primary Outcome ◽

Invasive Mechanical Ventilation ◽

Prophylactic Dose ◽

Dose Heparin ◽

The Mean ◽

Hospital Wards ◽

D Dimer

Abstract Objective To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. Design Randomised controlled, adaptive, open label clinical trial. Setting 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. Participants 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). Interventions Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. Main outcome measures The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. Results The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m 2 . At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). Conclusions In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. Trial registration ClinicalTrials.gov NCT04362085 .

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Escalation in Therapy Based on Intravenous Magnesium Sulfate Dosing in Pediatric Patients With Asthma Exacerbations

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-25.4.314 ◽

2020 ◽

Vol 25 (4) ◽

pp. 314-319

Author(s):

Christine A. Kapuscinski ◽

Sierra D. Stauber ◽

David J. Hutchinson

Keyword(s):

Mechanical Ventilation ◽

Magnesium Sulfate ◽

Adjunctive Therapy ◽

Primary Outcome ◽

Invasive Mechanical Ventilation ◽

Classification And Regression Tree ◽

Cart Analysis ◽

Non Invasive ◽

Asthma Exacerbations ◽

Intravenous Magnesium

OBJECTIVE Our objective was to compare doses of intravenous magnesium sulfate and their association with escalations in therapy in children and adolescents presenting to the emergency department with an asthma exacerbation. METHODS This was a retrospective cohort study among children who received both magnesium sulfate and standard of care therapy for asthma exacerbations. A classification and regression tree (CART) analysis was performed to identify a breakpoint in dose in which a difference in the primary outcome was present. The primary endpoint was need for escalation in therapy within 24 hours of initial magnesium sulfate dose, defined as need for invasive or non-invasive mechanical ventilation or need for adjunctive therapy, that is, epinephrine, terbutaline, aminophylline, theophylline, ketamine, heliox, or additional doses of magnesium sulfate. RESULTS A total of 210 patients were included in the study. A CART analysis identified that a breakpoint of 27 mg/kg of magnesium was associated with a difference in the primary outcome of escalation in therapy in patients <40 kg. A subgroup analysis of patients <40 kg (n = 149) found patients who received magnesium doses >27 mg/kg had a higher incidence of the primary outcome of escalation in therapy, 15 patients (18.3%) versus 3 patients (4.5%) in the ≤27-mg/kg/dose group (p = 0.011). CONCLUSIONS Our results demonstrate larger doses of magnesium sulfate are associated with an increased need for invasive or non-invasive mechanical ventilation or need for adjunctive therapy(ies). Our findings are limited by confounding factors that may have influenced this outcome in our population.

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Ambulatory care of non-invasive mechanical ventilation in COPD patients with global decompensated respiratory acidosis

Pneumologie ◽

10.1055/s-0037-1598429 ◽

2017 ◽

Vol 71 (S 01) ◽

pp. S1-S125

Author(s):

EJ Soto Hurtado ◽

P Gutiérrez Castaño ◽

JJ Torres ◽

MD Jiménez Fernández ◽

M Pérez Soriano ◽

...

Keyword(s):

Mechanical Ventilation ◽

Ambulatory Care ◽

Invasive Mechanical Ventilation ◽

Respiratory Acidosis ◽

Non Invasive ◽

Copd Patients

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Differences between non invasive mechanical ventilation in the hypoxemic and hypercapnic respiratory failure

10.1055/s-0039-1678119 ◽

2019 ◽

Author(s):

EJ Soto Hurtado ◽

MA López ◽

ES Lobera ◽

J Torres Jiménez ◽

JL de la Cruz Rios

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Invasive Mechanical Ventilation ◽

Hypercapnic Respiratory Failure ◽

Non Invasive

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Nasal High-Frequency Oscillatory Ventilation in Preterm Infants with Moderate Respiratory Distress Syndrome: A Multicenter Randomized Clinical Trial

Neonatology ◽

10.1159/000515226 ◽

2021 ◽

pp. 1-7

Author(s):

Xingwang Zhu ◽

Zhichun Feng ◽

Chengjun Liu ◽

Liping Shi ◽

Yuan Shi ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Distress Syndrome ◽

Preterm Infants ◽

High Frequency ◽

Primary Outcome ◽

Distress Syndrome ◽

Invasive Mechanical Ventilation ◽

Risk Difference ◽

High Frequency Oscillatory Ventilation ◽

High Frequency Oscillatory

Objective: To determine whether nasal high-frequency oscillatory ventilation (NHFOV) as a primary mode of respiratory support as compared with nasal continuous airway pressure (NCPAP) will reduce the need for invasive mechanical ventilation in preterm infants (260/7–336/7 weeks of gestational age [GA]) with respiratory distress syndrome (RDS). Methods: This multicenter randomized controlled trial was conducted in 18 tertiary neonatal intensive care units in China. A total of 302 preterm infants born at a GA of 260/7–336/7 weeks with a diagnosis of RDS were randomly assigned to either the NCPAP (n = 150) or the NHFOV (n = 152) group. The primary outcome was the need for invasive mechanical ventilation during the first 7 days after birth. Results: Treatment failure occurred in 15 of 152 infants (9.9%) in the NHFOV group and in 26 of 150 infants (17.3%) in the NCPAP group (95% CI of risk difference: −15.2 to 0.4, p = 0.06). In the subgroup analysis, NHFOV resulted in a significantly lower rate of treatment failure than did NCPAP in the strata of 26+0/7–29+6/7weeks of GA (11.9 vs. 32.4%, 95% CI of risk difference: −39.3 to −1.7, p = 0.03) and birth weight <1,500 g (10.4 vs. 29.6%, 95% CI of risk difference: −33.8 to −4.6, p = 0.01). The rate of thick secretions causing an airway obstruction was higher in the NHFOV group than in the NCPAP group (13.8 vs. 5.3%, 95% CI of risk difference: 1.9–15.1, p = 0.01). No significant differences in other secondary outcomes were found between the NHFOV and NCPAP groups. Conclusions: NHFOV was not superior to NCPAP with regard to the primary outcome when applied as the primary respiratory support for RDS in infants between 26+0/7 and 33+6/7 weeks of GA. In the subgroup analysis, NHFOV seemed to improve effectiveness than NCPAP in preterm infants <30 weeks of GA.

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Comparison of ETCO2 Value and Blood Gas PCO2 Value of Patients Receiving Non-invasive Mechanical Ventilation Treatment in Emergency Department

SN Comprehensive Clinical Medicine ◽

10.1007/s42399-021-00935-y ◽

2021 ◽

Author(s):

Hüseyin Uzunay ◽

Fatih Selvi ◽

Cihan Bedel ◽

Omer Faruk Karakoyun

Keyword(s):

Emergency Department ◽

Mechanical Ventilation ◽

Invasive Mechanical Ventilation ◽

Blood Gas ◽

Non Invasive

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Empiric use of anticoagulation in hospitalized patients with COVID-19: a propensity score-matched study of risks and benefits

Biomarker Research ◽

10.1186/s40364-021-00283-y ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Bo Yu ◽

Victor Perez Gutierrez ◽

Alex Carlos ◽

Gregory Hoge ◽

Anjana Pillai ◽

...

Keyword(s):

Mechanical Ventilation ◽

Propensity Score ◽

Propensity Score Matching ◽

Major Bleeding ◽

Risk Estimation ◽

Large Population ◽

Invasive Mechanical Ventilation ◽

Bleeding Risk ◽

Hospitalized Patients ◽

Significant Difference

Abstract Background Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. Methods We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. Results The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345–0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110–1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114–3.729, p = 0.016). Conclusion Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

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