Sie können Operatoren mit Ihrer Suchanfrage kombinieren, um diese noch präziser einzugrenzen. Klicken Sie auf den Suchoperator, um eine Erklärung seiner Funktionsweise anzuzeigen.
Findet Dokumente, in denen beide Begriffe in beliebiger Reihenfolge innerhalb von maximal n Worten zueinander stehen. Empfehlung: Wählen Sie zwischen 15 und 30 als maximale Wortanzahl (z.B. NEAR(hybrid, antrieb, 20)).
Findet Dokumente, in denen der Begriff in Wortvarianten vorkommt, wobei diese VOR, HINTER oder VOR und HINTER dem Suchbegriff anschließen können (z.B., leichtbau*, *leichtbau, *leichtbau*).
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
COVID-19
Coronavirus 2019
CRP
C-reactive protein
Although corticosteroid administration has been associated with improved outcomes in severe COVID-19 pneumonia, their ideal use remains undefined with a “one size fits all” approach used, irrespective of the individual inflammatory response [1]. Recent studies have highlighted distinct COVID-19 inflammatory phenotypes with differential responses to corticosteroids [2]. Our goal was to assess the feasibility and safety of an individualized, biomarker-guided corticosteroid dosing approach utilizing C-reactive protein (CRP) in patients with pneumonia and acute hypoxemic respiratory failure (AHRF). With the COVID-19 outbreak, a separate COVID-19 trial arm was created, which we report here.
This was a single-center, pilot randomized controlled trial conducted in Mayo Clinic, Rochester, Minnesota from March 2020 through November 2020. Patients with COVID-19 pneumonia and AHRF were randomized to biomarker-guided corticosteroid dosing versus usual care. In the intervention arm, corticosteroid dosing and duration was adjusted to daily CRP level. The dosing algorithm was extrapolated from prior retrospective data [3]. Corticosteroid use and dosing in the usual care arm was determined by the treating physician. Of note, there was a practice change related to corticosteroid administration during the enrollment period following the publication of the RECOVERY trial [4]. All patients had CRP and Troponin measurements on the day of enrollment and then daily for 5 days. The primary outcome was the feasibility of the trial protocol. Secondary outcomes included cumulative corticosteroid exposure, hospital-free days, oxygen-free days, and evidence of cardiac injury (troponin elevation, echocardiographic evidence of new cardiac dysfunction).
Anzeige
Of 41 patients enrolled, 19 were randomized to the intervention arm and 22 to the usual care arm. No significant differences were observed between groups with regards to age, sex, comorbidities, and oxygen delivery devices (see Table 1). Study treatment protocol was followed in 18 (95%) patients in the intervention arm. In the intention to treat analysis the intervention arm had more oxygen-free days (23.5 (21, 25) versus 21 (17, 25), p = 0.033) and hospital-free days (21 (18, 22) versus 18.5 (15, 21), p = 0.05) than the usual care arm. Daily distribution of CRP in both arms revealed significantly lower CRP levels on day 3 in the intervention arm compared to the usual care arm (see Fig. 1).
Table 1
Baseline patient demographics and clinical characteristics
Characteristic
Usual Care (N = 22)
Intervention (N = 19)
Sex, n (%)
Female
9 (41%)
8 (42%)
Male
13 (59%)
11 (58%)
Age (years), median (Q1, Q3)
60.0 (50.0, 66.0)
59.0 (51.0, 81.0)
Race, n (%)
Asian
2 (9%)
0 (0%)
Black or African American
0 (0%)
2 (10.5%)
Unknown/Not Reported
3 (14%)
2 (10.5%)
White
17 (77%)
15 (79%)
BMI (kg/m2), median (Q1, Q3)
32.3 (28.5, 39.1)
30.8 (27.2, 39.9)
Saturation/FIO2 Ratio
332 (267.4, 430.5)
339 (250, 423)
Oxygen delivery at randomization, n (%)
HFNC
7 (32%)
3 (16%)
Mechanical ventilation
1 (4%)
1 (5%)
Nasal Cannula
14 (64%)
11 (58%)
Room air
0 (0%)
4 (21%)
COPD, n (%)
0 (0%)
0 (0%)
Admitted to ICU at randomization, n (%)
10 (45%)
4 (21%)
Sepsis, n (%)
0 (0%)
0 (0%)
Diabetes, n (%)
5 (23%)
4 (21%)
Asthma, n (%)
4 (18%)
1 (5%)
Home oxygen use, n (%)
0 (0%)
0 (0%)
Dementia, n (%)
0 (0%)
1 (5%)
Fig. 1
Daily C-reactive protein distribution by arm. CRP: C-reactive Protein
Seventeen (90%) patients in the intervention arm received corticosteroids and 2 patients (due to low CRP levels) did not base on the CRP guided protocol. 11 (50%) patients in the usual care arm received corticosteroids. Steroid use was rare prior to the publication of RECOVERY trial in June 2020. After June 2020, patients in the usual care arm typically received fixed-dose dexamethasone.
When the analysis was restricted to patients that received steroids in both groups, the intervention arm (n = 17) had less cumulative steroid exposure [median 122 (102.0, 160.0.) versus 256 (128, 320) mg, p = 0.005], more oxygen-free days [23 (20, 25) versus 17 (8, 22), p = 0.032] and no difference in hospital-free days [21 (18, 22) versus 17 (7, 21), p = 0.06] than the usual care arm (n = 11).
The results of this single-center pilot randomized controlled clinical trial show that an individualized biomarker-guided corticosteroid dosing approach in pneumonia using CRP is feasible and safe with high adherence to the study protocol. Although not powered to detect differences in patient-centered outcomes, the individualized CRP-guided corticosteroid dosing approach was associated with increased oxygen-free days, hospital-free days, and a lower corticosteroid cumulative exposure in the intervention arm. This is the first study evaluating an individualized biomarker-guided strategy to inform corticosteroid dosing in COVID-19 pneumonia. The protocol outlined can provide a more precise strategy of adjunct drug delivery than the current one-size-fits-all approach. A larger, multicenter clinical trial is needed to determine the efficacy and safety of this approach.
Anzeige
Declarations
Ethics approval and consent to participate
This study was approved by the Mayo Clinic Institutional Review Board (IRB number: 18–010925) prior to its initiation. Written informed consent was obtained from all the patients or from a legal representative.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
COVID-19 Treatment Guidelines-NIH. (COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [11/11/21]).
2.
Sinha P, Furfaro D, Cummings MJ, et al. Latent class analysis reveals COVID-19-related acute respiratory distress syndrome subgroups with differential responses to corticosteroids. Am J Respir Crit Care Med. 2021;204(11):1274–85. https://doi.org/10.1164/rccm.202105-1302OC.CrossRefPubMed
3.
Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015;313(7):677–86. https://doi.org/10.1001/jama.2015.88.CrossRefPubMed
4.
Dexamethasone in Hospitalized Patients with Covid-19—Preliminary Report. New England Journal of Medicine 2020. https://doi.org/10.1056/NEJMoa2021436.
Den heißen Tee in der Hand und die Wärmflasche auf dem Bauch: Gerade im Winter bringt man solche Situationen im Allgemeinen mit Wohlbehangen in Verbindung. Ein chirurgisches Team warnt jedoch mit einer Serie von Verbrühungsfällen vor Unachtsamkeit.
Ketamin und Etomidat sind zwei Präparate, die häufig zur Blitzeinleitung für die Intubation kritisch Kranker verwendet werden. Welches von beiden ist effektiver? Zwei Studien haben das untersucht.
Ein fit und gesund erscheinender Mittfünfziger stellt sich mit plötzlich aufgetretener linksseitiger Schwäche, Taubheit und Ataxie in der Klinik vor. Sein Blutdruck beträgt 254/150 mmHg. Die Ursachensuche bleibt zunächst erfolglos. Die entscheidende Frage wird erst Wochen später gestellt.
Akute und chronische Kopfschmerzen nach hämorrhagischem Apoplex sind ein in Studien vernachlässigtes Symptom. US-Neurologen haben dazu eine systematische Übersicht mit Metaanalyse verfasst.
