scholarly journals Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2

Author(s):  
Russell M. Petrak ◽  
Nathan C. Skorodin ◽  
Nicholas W. Van Hise ◽  
Robert M. Fliegelman ◽  
Jonathan Pinsky ◽  
...  

AbstractBackgroundTocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2.MethodsWe evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between 3/13/20 and 4/16/20. This was a multi-center study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. In the absence of mechanical ventilation, the timing of the dose was related to the patient’s date of admission only.ResultsWe evaluated 145 patients. The average age was 58.1 years, 64% were male, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% expired, of which 43.9% were African American. Mechanical ventilation was required in 55.9%, of which 34.5% expired. Avoidance of MV (p value = 0.002) and increased survival (p value < 0.001) was statistically associated with early dosing.ConclusionsTocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill COVID-19 patients.SummaryUtilizing tocilizumab early in the treatment course of critically ill patients with COVID-19 resulted in significant decreases in mortality and the avoidance of mechanical ventilation.

2020 ◽  
Author(s):  
Russell M. Petrak ◽  
Nicholas W. Van Hise ◽  
Nathan C. Skorodin ◽  
Robert M. Fliegelman ◽  
Vishnu Chundi ◽  
...  

AbstractBackgroundSARS-CoV-2 is a novel coronavirus that has rapidly expanded to become a pandemic, resulting in millions of deaths worldwide. The cytokine storm is caused by the release of inflammatory agents and results in a physiologic disruption. Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2.MethodsThis was a multi-center study of patients infected with SARS-CoV-2, admitted between 3/13/20 and 4/16/20, requiring mechanical ventilation. Parameters that were evaluated included age, sex, race, usage of steroids, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was utilized for comparison (untreated).FindingsWe studied 118 patients who required mechanical ventilation. Eighty-one (81) received tocilizumab, compared to 37 who were untreated. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p=0.003). Dosing tocilizumab late was associated with an increased mortality compared to the untreated group (p=0.006).InterpretationEarly tocilizumab administration was associated with decreased mortality in critically ill SARS-Co-V-2 patients, but a potential detriment was suggested by dosing later in a patient’s course.FundingThis work did not receive outside funding or sponsorship.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14535-e14535
Author(s):  
Carlos Aliaga Macha ◽  
Thanya Runciman ◽  
Carlos F. Carracedo

e14535 Background: Inflammatory markers have been used as prognostic factors in multiple malignancies.In cancer patients, critically ill, the utility of these have limited data.The aim of our study is to determine whether neutrophil lymphocyte ratio (NLR) or lymphocyte platelet ratio(PLR) are prognostic factors for mortality in critically ill patients. Methods: We retrospectively analyzed data of 79 patients with solid tumors admitted to ICU at Sanna-Aliada Clinic between January 2018 to December 2018. Inflammatory markers results were obtained from laboratory tests performed during the first 24h of admission to ICU. Receiving operating characteristic (ROC) curves were constructed and the sensitivity, specificity, predictive values and probability indicators for the NLR and PLR. Results: A total of 79 patients were assessed, 39 women and 40 men. The average age was 60.28 years, median of 61 ( 18 to 91). 51.9% had metastatic disease. The most frequent places were lung 12 (15.2 %) and brain 9 (11,4%) . The main cause for admission to ICU was infectious disease (40.5%). The analysis of normality (Kolmogorov-Smirnov test) indicates that the variables age, hemoglobin, leukocytes, platelets, neutrophils, lymphocytes, have a normal deviation while the other variables: lactate, PCR, neutrophil to lymphocyte ratio (NLR) , Platelet to lymphocyte ratio (PLR) are not distributed normally. Regarding mortality, 44 patients were alive at 30 days (66.7%), and 30 (45.5%) were alive at 90 days. The average stay in the ICU was 8.43 days, with a median of 6, (SD 7.17, 1 to 40 days), 22.8% died in the ICU. The evaluation of PLR and NLR as a mortality marker is significant for the group of patients admitted to the ICU due to a noninfectious pathology, generating an area under the curve (AUC) of 0.706 for NLR (95% CI, 0.535 - 0.876, p-value = 0.035) and 0.767 for PLR (95% CI, 0.615-0.918; p-value = 0.006); the optimal cut point by Youden’s index for NLR was 8.29 and 267.94 for PLR (Sensitivity: 76%, Specificity: 67%). In contrast, the group with infectious pathology, the AUC was 0.47 for NLR (p = 0.78) and 0.42 for PLR (p = 0.44). The relationship of the biomarkers with stay in ICU was also evaluated, finding a statistically significant association with the lactate value (p = 0.024, Kruskal-Wallis) Conclusions: Inflammatory markers are useful as predictive markers of mortality in critically ill patients due to non-infectious causes. The lactate value serves as a predictive factor of stay in the ICU for all the patients. We suggest carrying out prospective studies to confirm the validity of our findings.


Author(s):  
Dr. Raghvendra Singh ◽  
Dr. Ramesh Kumar

Background: Pneumonia is the second most common nosocomial infection among critically ill patients, affecting 27% of all critically ill patients. Methods: The study was conducted in an intensive care unit (ICU) of a tertiary care centre. A total of 100 patients who were kept on mechanical ventilator were randomly selected. Cases included were patients of both sexes who were kept on mechanical ventilator for more than 48 h, having the age of >15 years. Patients who died or developed pneumonia within 48 h or those who were admitted with pneumonia at the time of admission and patients of ARDS (Acute Respiratory Distress Syndrome) were excluded from the study. Results: The mean duration of mechanical ventilation was found to be 12.3±3.1 days for the non-VAP group and 19.1 ±4.2 days for the VAP group that those requiring prolonged ventilator support (>15 days) had a significantly higher incidence of VAP (P-value, 0.001). Supine position and stuporous, comatose patients were found to be risk factors, having a high incidence of VAP, and proved to be statistically significant. Conclusion: Incidence is directly proportional to duration of mechanical ventilation and re-intubation is a strong risk factor for development of VAP. Therefore, duration of ventilation has to be reduced to get rid of morbidity and mortality associated with mechanical ventilation, which can be achieved by administering a proper weaning protocol and titrating sedation regimens as per the need of the patients. Keywords: Incidence, Infection, ICU


2020 ◽  
Author(s):  
Abhishek Goyal ◽  
Saurabh Saigal ◽  
Ankur Joshi ◽  
Dodda Brahmam ◽  
Yogesh Niwariya ◽  
...  

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Eleni Papoutsi ◽  
Vassilis G. Giannakoulis ◽  
Eleni Xourgia ◽  
Christina Routsi ◽  
Anastasia Kotanidou ◽  
...  

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Ines Schroeder ◽  
Michael Paal ◽  
Martin Winkels ◽  
Michael Irlbeck ◽  
...  

Abstract Background A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. Methods Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables. Results In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). Conclusion Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.


Author(s):  
Aurélie GOUEL-CHERON ◽  
Yoann ELMALEH ◽  
Camille COUFFIGNAL ◽  
Elie KANTOR ◽  
Simon MESLIN ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yongfang Zhou ◽  
Steven R. Holets ◽  
Man Li ◽  
Gustavo A. Cortes-Puentes ◽  
Todd J. Meyer ◽  
...  

AbstractPatient–ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.


2021 ◽  
Vol 21 (S2) ◽  
Author(s):  
Longxiang Su ◽  
Chun Liu ◽  
Fengxiang Chang ◽  
Bo Tang ◽  
Lin Han ◽  
...  

Abstract Background Analgesia and sedation therapy are commonly used for critically ill patients, especially mechanically ventilated patients. From the initial nonsedation programs to deep sedation and then to on-demand sedation, the understanding of sedation therapy continues to deepen. However, according to different patient’s condition, understanding the individual patient’s depth of sedation needs remains unclear. Methods The public open source critical illness database Medical Information Mart for Intensive Care III was used in this study. Latent profile analysis was used as a clustering method to classify mechanically ventilated patients based on 36 variables. Principal component analysis dimensionality reduction was used to select the most influential variables. The ROC curve was used to evaluate the classification accuracy of the model. Results Based on 36 characteristic variables, we divided patients undergoing mechanical ventilation and sedation and analgesia into two categories with different mortality rates, then further reduced the dimensionality of the data and obtained the 9 variables that had the greatest impact on classification, most of which were ventilator parameters. According to the Richmond-ASS scores, the two phenotypes of patients had different degrees of sedation and analgesia, and the corresponding ventilator parameters were also significantly different. We divided the validation cohort into three different levels of sedation, revealing that patients with high ventilator conditions needed a deeper level of sedation, while patients with low ventilator conditions required reduction in the depth of sedation as soon as possible to promote recovery and avoid reinjury. Conclusion Through latent profile analysis and dimensionality reduction, we divided patients treated with mechanical ventilation and sedation and analgesia into two categories with different mortalities and obtained 9 variables that had the greatest impact on classification, which revealed that the depth of sedation was limited by the condition of the respiratory system.


Sign in / Sign up

Export Citation Format

Share Document