scholarly journals Effective therapy regimens for COVID-19 pneumonia in critically ill patients with the development of the cytokine storm syndrome.

2020 ◽  
Author(s):  
Stanislav Serafimov
Keyword(s):  
Immune System ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Large Scale ◽  
Severe Pneumonia ◽  
Effective Therapy ◽  
Low Doses ◽  
Cytokine Storm ◽  
Treatment Regimens ◽  
Large Scale Study

The main reason for the development of severe pneumonia in patients with COVID‑19 is apparently injury of the endothelium by the virus and the immune system, which leads to the development of massive microthrombosis. We believe that it is very important to prescribe anticoagulants to COVID-19 patients as early as possible and to administer prolonged low doses of glucocorticoids at certain indicators. These treatment regimens are expected to reduce the mortality caused by COVID‑19. Perhaps it is necessary to be very careful about the administration of IL-6 inhibitors. We assume that the main indicators for the administration of IL-6 inhibitors are the following indicators: CRP > 150 mg/L, IL-6 in the blood > 40 pc/mL, procalcitonin < 0.5 μg/L. To confirm our hypotheses, a large-scale study is required.

Hydrocortisone vs Tocilizumab Effects on Cytokine Storm in Critically Ill Patients with COVID-19.

2020 ◽  
Author(s):  
Maria Vargas ◽  
Pasquale Buonanno ◽  
Carmine Iacovazzo ◽  
Gaetano Di Spigna ◽  
Daniela Spalletti ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Severe Pneumonia ◽  
Cytokine Storm ◽  
Tnf Α ◽  
Speed Up ◽  
The Impact ◽  
Late Stages

Abstract Introduction: Patients with severe pneumonia due COVID-19 are reported to have substantially lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines. In the late stages of COVID-19, cytokine storms are the mainly cause of disease progression and death. We performed a prospective observational study to evaluate the impact of tocilizumab and hydrocortisone on cytokine storm in critically ill patients with COVID-19.Methods: We included all adult patients with laboratory-confirmed COVID-19 infection and severe respiratory failure admitted to our ICU from March 10 to April 30. As therapeutic options, patients received tocilizumab od hydrocortisone. The primary end point was the evaluation of cytokine storm in terms of variation of the IL-6 and IL-6R, sgp130 and TNF-α concentrations during time to different treatment.Results: Eight patients received tocilizumab while 15 patients received hydrocortisone. IL-6 levels were lower in the hydrocortisone group with statistical significance was found at the days 2, 3, 8 and 9. The levels of IL-6R were lower during the days in the hydrocortisone group with statistical significance at days 1, 2, 3, 4, 5, 6, 8 and 10. Hydrocortisone group had higher levels of TNF-α at days 2, 3 and 4. The levels of sgo130 between tocilizumab and hydrocortisone groups were not statistically different during the days.Conclusions: In critically ill patients with severe COVID-19, the use of hydrocortisone allowed a better control of the cytokine storms, was further associated to less days of curarization, pronation and length of stay in ICU, and speed up the time to get negative RT-PCR swab.

Coronavirus disease 2019 in critically ill patients: can we re-program the immune system? A primer for Intensivists

2020 ◽  
Vol 86 (11) ◽  
Author(s):  
Fiorenza Ferrari ◽  
Federico Visconti ◽  
Mara De Amici ◽  
Angelo Guglielmi ◽  
Costanza N. Colombo ◽  
...  
Keyword(s):  
Immune System ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
System A

scholarly journals Can the cytokine adsorber CytoSorb® help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Ines Schroeder ◽  
Michael Paal ◽  
Martin Winkels ◽  
Michael Irlbeck ◽  
...  
Keyword(s):  
Propensity Score ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Wilcoxon Test ◽  
Relative Reduction ◽  
Cytokine Storm ◽  
Saps Ii ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

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.

scholarly journals Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia

2021 ◽  
Vol 8 ◽  
Author(s):  
Peter Jirak ◽  
Zornitsa Shomanova ◽  
Robert Larbig ◽  
Daniel Dankl ◽  
Nino Frank ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Severe Pneumonia ◽  
Thromboembolic Events ◽  
Therapeutic Anticoagulation ◽  
Tertiary Hospitals ◽  
Ventricular Tachycardias ◽  
Disease Specific ◽  
Rhythm Monitoring

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins.Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%).Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

Effects of Insulin and Glycaemic Management on Neuromuscular Function

2014 ◽  
Author(s):  
Greet Hermans
Keyword(s):  
Insulin Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Large Scale ◽  
Prolonged Mechanical Ventilation ◽  
Protective Action ◽  
Neuromuscular Function ◽  
Clinical Observations ◽  
Potential Benefits ◽  
Electrophysiological Findings

Observational studies have indicated an association between stress-induced hyperglycaemia and neuromuscular complications in critically ill patients. This observation is further supported by electrophysiological findings from two randomized controlled trials which suggested that titrating insulin therapy to achieve a normal blood glucose has a beneficial effect on neuromuscular function, associated with a reduced need for prolonged mechanical ventilation. The underlying pathophysiological mechanisms explaining these clinical observations are not well understood. There is no clear evidence that insulin has anabolic effects on muscle nor that it provides mitochondrial protection. It is possible that the effect of insulin therapy reflects a protective action on peripheral nerves; however, this hypothesis awaits confirmation. Overall, the potential benefits on neuromuscular function must be considered in light of large-scale randomized trials which demonstrate equivalent or worse outcome in critically ill patients managed with intensive insulin therapy.

scholarly journals Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e036047
Author(s):  
Vincent Issac Lau ◽  
Deborah J Cook ◽  
Robert Fowler ◽  
Bram Rochwerg ◽  
Jennie Johnstone ◽  
...  
Keyword(s):  
Incremental Cost ◽  
Usual Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Severe Pneumonia ◽  
Sensitivity Analyses ◽  
Public Healthcare ◽  
Surgical Trauma ◽  
Unit Costs ◽  
Individual Site

IntroductionVentilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysisThe objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and disseminationStudy approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration numberNCT01782755; Pre-results.

scholarly journals Development of an Immunoassay for the Kidney-Specific Protein myo-Inositol Oxygenase, a Potential Biomarker of Acute Kidney Injury

2014 ◽  
Vol 60 (5) ◽  
pp. 747-757 ◽  
Author(s):  
Joseph P Gaut ◽  
Dan L Crimmins ◽  
Matt F Ohlendorf ◽  
Christina M Lockwood ◽  
Terry A Griest ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Large Scale ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Specific Protein ◽  
Creatinine Concentration ◽  
Potential Biomarker ◽  
Mouse Tissues

Abstract BACKGROUND Acute kidney injury (AKI) affects 45% of critically ill patients, resulting in increased morbidity and mortality. The diagnostic standard, plasma creatinine, is nonspecific and may not increase until days after injury. There is significant need for a renal-specific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renal-specific biomarker of AKI. METHODS We analyzed gene expression data from normal mouse tissues to identify kidney-specific genes, one of which was Miox. We generated monoclonal antibodies to recombinant myo-inositol oxygenase (MIOX) and developed an immunoassay to quantify MIOX in plasma. The immunoassay was tested in animals and retrospectively in patients with and without AKI. RESULTS Kidney tissue specificity of MIOX was supported by Western blot. Immunohistochemistry localized MIOX to the proximal renal tubule. Serum MIOX, undetectable at baseline, increased 24 h following AKI in mice. Plasma MIOX was increased in critically ill patients with AKI [mean (SD) 12.4 (4.3) ng/mL, n = 42] compared with patients without AKI [0.5 (0.3) ng/mL, n = 17] and was highest in patients with oliguric AKI [20.2 (7.5) ng/mL, n = 23]. Plasma MIOX increased 54.3 (3.8) h before the increase in creatinine. CONCLUSIONS MIOX is a renal-specific, proximal tubule protein that is increased in serum of animals and plasma of critically ill patients with AKI. MIOX preceded the increases in creatinine concentration by approximately 2 days in human patients. Large-scale studies are warranted to further investigate MIOX as an AKI biomarker.

Dopamine and Intraocular Pressure in Critically Ill Patients

2000 ◽  
Vol 93 (6) ◽  
pp. 1398-1400 ◽  
Author(s):  
Peter C. Brath ◽  
Drew A. MacGregor ◽  
Jerry G. Ford ◽  
Richard C. Prielipp
Keyword(s):  
Intensive Care Unit ◽  
Intraocular Pressure ◽  
Ocular Hypertension ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Receptor Agonist ◽  
Low Doses ◽  
Mechanically Ventilated ◽  
Dopamine Infusion ◽  
Potent Agonist

Background A recently released dopamine-1 receptor agonist, fenoldopam, increases intraocular pressure (IOP) in both healthy volunteers and patients with chronic ocular hypertension. Dopamine, a potent agonist at both dopamine-1 and -2 receptors, is frequently infused in critically ill patients for its inotropic, renal vasodilatory, and natriuretic effects. The authors hypothesized that low doses of dopamine would significantly increase IOP. Methods Patients in the intensive care unit who were currently receiving dopamine infusions of less than 5 microg x kg(-1) x min(-1) were studied After local ocular anesthesia was obtained, baseline IOP was measured in each eye with a hand-held tonometer. IOP was then determined after dopamine was discontinued. Results Twenty-three patients received a mean dopamine infusion of 2.6 +/- 0.2 microg x kg(-1) x min(-1). Twelve of the 23 patients were receiving mechanical ventilation during the study. Mean IOPs in nonventilated patients (n = 11) off dopamine were 13.1 +/- 0.9 mmHg (left eye) and 12.6 +/- 0.9 mmHg (right eye). Mean IOPs for the same patients receiving dopamine were significantly higher at 16.1 +/- 0.9 mmHg (left eye) and 15.9 +/- 1.1 mmHg (right eye). Mean IOPs in intubated patients (n = 12) off dopamine were 12.3 +/- 0.7 mmHg (left eye) and 12.5 +/- 1.2 mmHg (right eye). Mean IOPs for the same patients while receiving dopamine were significantly higher in intubated patients at 17.8 +/- 1.3 mmHg (left eye) and 17.3 +/- 1.3 mmHg (right eye). The average mean elevation in IOP in patients while receiving dopamine was significantly higher in intubated patients as compared with nonintubated patients (5.2 +/- 0.9 mmHg vs. 3.1 +/- 0.6 mmHg). Conclusions Commonly used doses of dopamine are associated with increased IOP in critically ill patients. Although normal patients should be able to tolerate this elevation safely for several weeks, there may be a potential risk in patients with preexisting glaucomatous nerve damage or ocular hypertension, especially if they are sedated and mechanically ventilated.

scholarly journals COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and may be modified by dexamethasone

2021 ◽  
Author(s):  
Aartik Sarma ◽  
Stephanie A. Christenson ◽  
Eran Mick ◽  
Catherine DeVoe ◽  
Thomas Deiss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Tract ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Host Response ◽  
Lower Respiratory Tract ◽  
Transcriptional Profiling ◽  
Cytokine Storm

AbstractWe performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression.

scholarly journals Early Tocilizumab Dosing is Associated with Improved Survival In Critically Ill Patients Infected With Sars-CoV-2

2020 ◽  
Author(s):  
Russell M. Petrak ◽  
Nicholas W. Van Hise ◽  
Nathan C. Skorodin ◽  
Robert M. Fliegelman ◽  
Vishnu Chundi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Markers ◽  
Standard Of Care ◽  
Control Group ◽  
Cytokine Storm ◽  
Novel Coronavirus ◽  
Multi Center Study ◽  
Center Study

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.

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