scholarly journals 553. Critically Ill patients Receiving Tocilizumab Compared With Those Not Receiving Tocilizumab for Treatment of COVID-19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S342-S342
Author(s):  
Michael Leonard ◽  
anthony Asher ◽  
Banks Kooken ◽  
Erin Donahue ◽  
james Symanowski ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Critically Ill ◽  
Symptom Onset ◽  
Critically Ill Patients ◽  
Immune Modulation ◽  
Case Series ◽  
Supplemental Oxygen ◽  
Retrospective Case ◽  
Protein Levels ◽  
The Impact

Abstract Background Background:: Immune modulation in patients with clinical features suggestive of a cytokine release syndrome (CRS) has become a pharmacologic target for potential treatment of COVID-19 and prevention of ARDS. Tocilizumab is an IL-6 receptor blocker FDA-approved for chimeric antigen receptor (CAR) T cell-induced severe or life-threatening CRS. The objective of this study was to describe clinical outcomes associated with tocilizumab compared with those not receiving tocilizumab in critically ill patients with severe COVID-19. Methods Methods: Retrospective case series of 49 adult patients admitted to an intensive care unit with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients receiving tocilizumab were compared with those not receiving tocilizumab. The primary outcome was clinical improvement (decrease in supplemental oxygen requirement, discharge from ICU, or live discharge from hospital). Secondary endpoints included mortality and frequency of extubation. All comparative endpoints were assessed at 2 weeks after ICU admission. Results Results: 49 patients were identified with SARS-CoV-2 who were admitted to an ICU, 16 received tocilizumab. Baseline characteristics were similar; most were African American males with comorbidities such as obesity, cardiovascular disease, and diabetes. The time from symptom onset to positive test and subsequent intubation were similar (4 and 7 days, respectively). 75% received one dose (all received 8 mg/kg). The median time from symptom onset to tocilizumab administration was 11 days. In patients receiving tocilizumab compared with those not receiving tocilizumab, there were similar rates of clinical improvement (44% versus 61%, p=0.27), extubation (31% versus 45%, p=0.60), and mortality (18% versus 19%, p >0.99, respectively). 81% of the tocilizumab group had resolution of fever and 75% had improvement in C-reactive protein levels. Conclusion Conclusion: In this study of patients with progressed disease, outcomes were similar regardless of receipt of tocilizumab. Randomized controlled trials are needed to assess the impact of earlier administration and identify clinical characteristics to assist with selection of appropriate patients who may benefit from tocilizumab. Disclosures All Authors: No reported disclosures

scholarly journals Tocilizumab for the Critically Ill With Severe COVID-19: A Community Hospital Case Series

2021 ◽  
pp. 089719002110023
Author(s):  
Matt G. McKenzie ◽  
Yeunju (Michelle) Lee ◽  
Julin Mathew ◽  
Megan Anderson ◽  
Alison T. Vo ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Community Hospital ◽  
Hospital Setting ◽  
Case Series ◽  
Community Hospitals ◽  
Retrospective Case ◽  
The Mean ◽  
Present On Admission

Objective: To evaluate the use of tocilizumab in a community hospital setting for critically ill patients with severe COVID-19. Design: A retrospective case series Setting: Five community hospitals within 1 urban health system Patients: Adult patients whom received tocilizumab between March 27th, 2020 to April 30th, 2020 for severe COVID-19. Interventions: None. Measurements and Main Results Sixteen patients in total were evaluated from the 5 community hospitals. The mean (± SD) age of the patients was 53.9 ± 9.2 years, 56% were men, and the most common comorbidities present on admission were hypertension (31%) and diabetes mellitus (25%). All patients received at least 1 other treatment modality for COVID-19 (steroids, hydroxychloroquine, or convaslescent plasma). Additionally, all patients on admission to intensive care units had severe COVID-19 with 56% requiring mechanical ventilation with a pre-tocilizumab median (IQR) Pao2: Fio2 of 84 (69 – 108.6), 19% requiring vasopressor support, and inflammatory markers (CRP, LDH, ferritin, and IL-6) were elevated. The median (IQR) tocilizumab dose was 400 mg (400-600) which correlated with a weight-based mean (± SD) dose of 5.4 mg/kg ± 1.3. Of the 16 patients that received tocilizumab, 8 (50%) were discharged home, 7 (44%) died, and 1 (6%) was still hospitalized at the end of data collection. Patients who died were more likely to be older 62 ± 2 years, female (57%), had a higher rate of mechanical ventilation (86%) and vasopressors (43%) use at baseline, and had a higher median (IQR) IL-6 level prior to tocilizumab administration 550 pg/mL (IQR 83-1924). There were no reported adverse drug reactions reported after the administration of tocilizumab for any patient. Conclusions: Our findings do not support the effectiveness of tocilizumab in treatment of severe COVID-19 infection in critically ill patients.

scholarly journals 554. Early Clinical Outcomes with Tocilizumab for Covid-19: A Two-Center Retrospective Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S342-S343
Author(s):  
Steven Smoke ◽  
Karan Raja ◽  
Patrick Hilden ◽  
Nicole Daniel
Keyword(s):  
Clinical Improvement ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Univariate Analysis ◽  
Supplemental Oxygen ◽  
T Cell Therapy ◽  
Car T Cell Therapy ◽  
Car T ◽  
Study Sites ◽  
Early Clinical Outcomes

Abstract Background Severe Covid-19 is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an IL-6 inhibitor, effective in treating CRS secondary to CAR-T cell therapy. The efficacy of tocilizumab in treating Covid-19 is unknown. Methods This was a retrospective cohort study conducted at two hospitals in northern New Jersey. All patients treated with tocilizumab for confirmed or suspected Covid-19 between the dates of 3/10/20 and 4/9/20 at the study sites were included. The primary endpoint was clinical improvement on day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not. Results Forty five severe and critically ill patients treated with tocilizumab for Covid-19 were evaluated. Eleven (24%), 22 (49%) and 12 (27%) patients improved, had no change and worsened by day 7 after treatment, respectively. Lower WBC and LDH at the time of drug administration as well as shorter time from supplemental oxygen initiation to dose were significantly associated with clinical improvement in the univariate analysis. Conclusion Tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with Covid-19. Disclosures All Authors: No reported disclosures

scholarly journals Outcomes of non-COVID-19 critically ill patients during the COVID-19 pandemic

2021 ◽  
Author(s):  
Răzvan Bologheanu ◽  
Mathias Maleczek ◽  
Daniel Laxar ◽  
Oliver Kimberger
Keyword(s):  
Intensive Care ◽  
Length Of Stay ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Medical Specialty ◽  
Routine Care ◽  
Treatment Pathways ◽  
Icu Length Of Stay ◽  
Matched Study ◽  
The Impact

Summary Background Coronavirus disease 2019 (COVID-19) disrupts routine care and alters treatment pathways in every medical specialty, including intensive care medicine, which has been at the core of the pandemic response. The impact of the pandemic is inevitably not limited to patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their outcomes; however, the impact of COVID-19 on intensive care has not yet been analyzed. Methods The objective of this propensity score-matched study was to compare the clinical outcomes of non-COVID-19 critically ill patients with the outcomes of prepandemic patients. Critically ill, non-COVID-19 patients admitted to the intensive care unit (ICU) during the first wave of the pandemic were matched with patients admitted in the previous year. Mortality, length of stay, and rate of readmission were compared between the two groups after matching. Results A total of 211 critically ill SARS-CoV‑2 negative patients admitted between 13 March 2020 and 16 May 2020 were matched to 211 controls, selected from a matching pool of 1421 eligible patients admitted to the ICU in 2019. After matching, the outcomes were not significantly different between the two groups: ICU mortality was 5.2% in 2019 and 8.5% in 2020, p = 0.248, while intrahospital mortality was 10.9% in 2019 and 14.2% in 2020, p = 0.378. The median ICU length of stay was similar in 2019: 4 days (IQR 2–6) compared to 2020: 4 days (IQR 2–7), p = 0.196. The rate of ICU readmission was 15.6% in 2019 and 10.9% in 2020, p = 0.344. Conclusion In this retrospective single center study, mortality, ICU length of stay, and rate of ICU readmission did not differ significantly between patients admitted to the ICU during the implementation of hospital-wide COVID-19 contingency planning and patients admitted to the ICU before the pandemic.

scholarly journals SARS-CoV-2 and Cytomegalovirus Co-Infections—A Case Series of Critically Ill Patients

2021 ◽  
Vol 10 (13) ◽  
pp. 2792
Author(s):  
Patrícia Moniz ◽  
Sérgio Brito ◽  
Pedro Póvoa
Keyword(s):  
Intensive Care Unit ◽  
Critically Ill ◽  
Immune Suppression ◽  
Clinical Course ◽  
Health Care Systems ◽  
Case Series ◽  
Confounding Factors ◽  
Care Systems ◽  
The Impact ◽  
Cmv Reactivation

The SARS-CoV-2 pandemic has placed great strain on the most developed of health care systems, especially in the context of critical care. Although co-infections with cytomegalovirus (CMV) are frequent in the critically ill due to underlying immune suppression of multiple causes, the impact on COVID-19 patients remains unclear. Furthermore, severe COVID-19 has recently been associated with significant immune suppression, and this may in turn impact CMV reactivation, possibly contributing to clinical course. Nevertheless, multiple confounding factors in these patients will certainly challenge upcoming research. The authors present a case series of five patients admitted to the intensive care unit (ICU) in the context of respiratory failure due to severe COVID-19. All patients evolved with CMV reactivation during ICU stay.

scholarly journals Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured Versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 557
Author(s):  
Matthias Gijsen ◽  
Erwin Dreesen ◽  
Ruth Van Daele ◽  
Pieter Annaert ◽  
Yves Debaveye ◽  
...  
Keyword(s):  
Renal Function ◽  
Cohort Study ◽  
Protein Binding ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Observational Cohort Study ◽  
Target Attainment ◽  
Binding Model ◽  
Observational Cohort ◽  
The Impact

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

A Systematic Review of Anticoagulation Strategies for Patients With Atrial Fibrillation in Critical Care.

2021 ◽  
Author(s):  
Alexandra Jayne Nelson ◽  
Brian W Johnston ◽  
Alicia Achiaa Charlotte Waite ◽  
Gedeon Lemma ◽  
Ingeborg Dorothea Welters
Keyword(s):  
Atrial Fibrillation ◽  
Critical Care ◽  
Critically Ill ◽  
Major Bleeding ◽  
Critically Ill Patients ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
The Impact ◽  
Anticoagulated Patients

Background. Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes for general critical care patients with AF. Our aim was to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for AF. Methodology. A systematic literature search was conducted using MEDLINE, EMBASE, CENTRAL and PubMed databases. Studies reporting anticoagulation strategies for AF in adults admitted to a general critical care setting were assessed for inclusion. Results. Four studies were selected for data extraction. A total of 44087 patients were identified with AF, of which 17.8-49.4% received anticoagulation. The reported incidence of thromboembolic events was 0-1.4% for anticoagulated patients, and 0-1.3% in non-anticoagulated patients. Major bleeding events were reported in three studies and occurred in 7.2-8.6% of the anticoagulated patients and up to 7.1% of the non-anticoagulated patients. Conclusions. There was an increased incidence of major bleeding events in anticoagulated patients with AF in critical care compared to non-anticoagulated patients. There was no significant difference in the incidence of reported thromboembolic events within studies, between patients who did and did not receive anticoagulation. However, the outcomes reported within studies were not standardised, therefore, the generalisability of our results to the general critical care population remains unclear. Further data is required to facilitate an evidence-based assessment of the risks and benefits of anticoagulation for critically ill patients with AF.

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