Anesthesia: Essays and Researches  Login  | Users Online: 1730 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Home | About us | Editorial board | Ahead of print | Search | Current Issue | Archives | Submit article | Instructions | Copyright form | Subscribe | Advertise | Contacts


 
Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 15  |  Issue : 1  |  Page : 62-66  

Role of dexamethasone on oxygen requirement, mortality, and survival incidence among COVID-19 patients: Quasi-experimental study


Department of Anaesthesia, Sri Guru Ram Dass Institute of Medical Sciences and Research, Amritsar, Punjab, India

Date of Submission25-May-2021
Date of Acceptance18-Jun-2021
Date of Web Publication30-Aug-2021

Correspondence Address:
Dr. Lakshmi Mahajan
Associate Professor, Department of Anaesthesiology and Critical Care, SGRD Medical College and Hospital, Amritsar, Punjab
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.aer_70_21

Rights and Permissions
   Abstract 

Background: Patients diagnosed with coronavirus disease 2019 (COVID-19) are often prone to developing systemic inflammation which eventually causes damage to the lungs and other important organs. Randomized open-label control trials carried out in the different parts of the world have highlighted the importance of corticosteroids for treating such patients. Materials and Methods: The current quasi-experimental study was based on COVID-19-infected patients with oxygen saturation <92% and evidence of pneumonia confirmed through radiological examination. Study participants in Group A received standard care, while those in Group B received standard care along with 6 mg intravenous dexamethasone for 10 days (or until discharge, if earlier). The clinical status of the study participants was assessed on day 7 and day 14 on a 6-point ordinal scale. Results: It was observed from the study that there was reduction in the intensive care unit (ICU) stay and mortality among the study participants requiring high-flow oxygen or noninvasive ventilation in Group B as compared to Group A. After 7 days of treatment, 50% of the study participants in Group B got discharged as compared to 15% of the study participants in Group A. The number of study participants requiring mechanical ventilation remained 1 in Group B as compared to 5 in Group A. After the completion of treatment schedule, 91% study participants were discharged. There was 1 case of mortality reported in Group B as compared to 6 cases of mortality in Group A. Conclusions: The current study highlighted that fewer number of COVID-19-positive study participants in Group B required high-flow oxygen supplementation and noninvasive positive pressure ventilation as compared to those included in Group A. The corticosteroid treatment also reduced the number of ICU transfer and mortality.

Keywords: Coronavirus, severe acute respiratory syndrome coronavirus 2, COVID, coronavirus disease 2019, dexamethasone


How to cite this article:
Mahajan L, Singh AP, Singla A, Singh G. Role of dexamethasone on oxygen requirement, mortality, and survival incidence among COVID-19 patients: Quasi-experimental study. Anesth Essays Res 2021;15:62-6

How to cite this URL:
Mahajan L, Singh AP, Singla A, Singh G. Role of dexamethasone on oxygen requirement, mortality, and survival incidence among COVID-19 patients: Quasi-experimental study. Anesth Essays Res [serial online] 2021 [cited 2021 Nov 30];15:62-6. Available from: https://www.aeronline.org/text.asp?2021/15/1/62/325027


   Introduction Top


Coronavirus disease 2019 (COVID-19) is a respiratory tract infection which was first reported in the city of Wuhan, China, in the year 2019. Genetic sequencing of the virus suggests that it is a betacoronavirus closely linked to the severe acute respiratory syndrome (SARS) virus.[1] The severity of COVID-19 symptoms can range from asymptomatic or mild to severe respiratory illness with hypoxemic respiratory failure requiring ventilator support. These patients often experience symptoms such as shortness of breath and pneumonia after the beginning of symptoms. As per the details issued by the World Health Organization, 14% of the patients develop severe symptoms of the disease, often requiring external oxygen supply, or admission to the intensive care unit (ICU).[1] This condition is further complicated by the occurrence of multiorgan injury, sepsis, or acute respiratory distress syndrome (ARDS).[2] Patients with severe symptoms and elevated levels of inflammatory markers such as C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, and interleukin-6 often suffer from inflammation-induced injury.[3],[4] The heightened inflammatory response in patients highlighted the use of corticosteroids.

Literature published earlier suggested that systemic corticosteroids did not have any effects on mortality and could increase viral replication and prolong viral shedding. The drug was associated with an increase in the risk of worsening clinical status, delayed viral clearance, and adverse events.[5],[6],[7] Clinical trials held later evidenced an improvement in the clinical outcomes in COVID-19 patients treated with corticosteroids, mainly in severe COVID-19 condition requiring external respiratory support.[8] The Infectious Diseases Society of America (IDSA) guidelines suggested the use of glucocorticoids for patients with severe COVID-19 infection with SpO2 requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation. The IDSA recommends against the use of glucocorticoids for those with COVID-19 without hypoxemia and not requiring supplemental oxygen.[9]

Literature survey has highlighted the fact that the severe infection of COVID-19 is mainly caused due to hypersensitivity of the immune system of the patient. This condition is referred to as cytokine storm and is life threatening, which if untreated, may cause damage to the lungs of the patient. This condition is often treated with the help of corticosteroid such as dexamethasone that acts as an anti-inflammatory agent against cytokine storm in critical COVID-19 patients.

The present study is designed to observe the role of dexamethasone on overall mortality, oxygen support based on either HFNO/noninvasive ventilation (NIV), requirement of invasive mechanical ventilation during hospitalization in critically ill COVID-19 patients who were admitted in the ICU of the tertiary care hospital and receiving standard care or dexamethasone treatment.


   Materials and Methods Top


Study population

Consecutive patients hospitalized in the tertiary care center from May, 2020 to July, 2020 who fulfilled the inclusion and exclusion criteria were enrolled in the study. The inclusion criteria are age of year, oxygen saturation while breathing room air (SatO2) <92% and requiring oxygen flow ≥4L.min−1, tachypnea >30/min, difficulty in breathing, and laboratory-confirmed COVID-19 infection by reverse transcription-polymerase chain reaction (RT-PCR; SARS coronavirus 2 [CoV-2] real-time PCR).

Pregnant or breastfeeding women, moribund status, hypersensitivity to dexamethasone or to any of the excipients, multiorgan failure, patients already on mechanical ventilation for active and untreated bacterial, fungal or parasitic infection at the time of admission were excluded from the study.

Study design

The quasi-experimental study was carried out on the patients who were admitted in the ICU of the tertiary care hospital due to severe COVID-19 infection after taking prior institutional ethical approval. The patients were enrolled in the study after taking written and verbal informed consent from them or their legal representatives. The study participants who fulfilled the exclusion and inclusion criteria were enrolled in the study from August, 2020 to October and were divided into two groups. Group A comprised of patients who received standard care of treatment, while those in Group B received standard care along with 6 mg dexamethasone once daily for 10 days or till the patient achieved negative nucleic acid status, whichever was earlier. Decision of administering dexamethasone was solely on the primary medical team. Patients were followed until death or discharge from the hospital for 14 days.

Outcome measures

Patients receiving dexamethasone were continuously monitored for any risk of reactivation of latent infections. All participants were monitored for narrow control of respiratory frequency and oxygen saturation (SatO2 ≤92% or oxygen administered by nasal prongs to keep SatO2 above 95%). In case, this could not be achieved, venturi masks up to FiO2 0.35 were used. If the patient needed FiO2 >0.40 for keeping SatO2 >92%, then a high-flow nasal supplementation with adjusted levels of FiO2 was started. In case of failure to keep SatO2 >95% in these conditions, NIV was considered. If the patient could not maintain SatO2 >95% with NIV, then ICU admission and invasive mechanical ventilation were considered.

The clinical status of the patients was assessed on day 7 and 14 on a 6-point ordinal scale including (1) do not require hospitalization, (2) hospitalized, requiring low supplemental oxygen, (3) patients requiring high-flow oxygen, (4) patient requiring NIV, (5) requiring or receiving mechanical ventilation, (6) death, if a patient was discharged before day, and (7) it was recorded as not hospitalized. The final analysis of the study was the requirement of ventilation or in-hospital death and the time required for clinical improvement. Improvement was assessed by reduction in the requirement of oxygen supplementation. Oxygen-support requirements, adverse events, and laboratory values were assessed in follow-up routine. Any change in the requirements of oxygen support, or mechanical ventilation, noninvasive positive pressure ventilation (NIPPV) adverse events, death, etc., were recorded for each patient in Group A and Group B.

Statistical analysis

Descriptive analysis was performed to compare baseline characteristics of participants who were receiving dexamethasone and those who were receiving standard care using the statistical package for the social sciences (SPSS) version 23.0.


   Results Top


Ninety-seven consecutively admitted COVID-19-positive patients were evaluated for inclusion, 10 were excluded because RT-PCR was negative for SARS-CoV-2 and 8 because SatO2 was not lower than 92%. Among the remaining patients included for analysis, 40 were receiving dexamethasone (placed in Group B) and 39 were receiving standard care and were put in Group A.

The median age was 51 years in both groups [Table 1]. In the dexamethasone group, 21 participants were hypertensive as compared to 15 in Group A (52.5% vs. 38.5%). 27 (67.5%) participants were diabetic, 1 (2.5%) suffered from chronic kidney disease, 4 (10%) had chronic artery disease, and 1 (2.5%) had chronic obstructive pulmonary disease in Group B, while 23 (58.9%) participants were diabetic, 2 (5.1%) suffered from chronic kidney, and 4 (10.2%) had chronic artery disease in Group A. Two participants in dexamethasone as well as Group A had hypothyroidism and one participant in Group A had cerebrovascular accident. The composite endpoint (ICU admission or death) occurred in 15.4% of participants, i.e. 5 (12.8%) out of 39 participants in Group A and in 1 (2.5%) out of 40 participants in Group B [Table 2].
Table 1: Demographic profile of study participants

Click here to view
Table 2: Clinical baseline characteristics of study participants

Click here to view


Among all the participants, cumulative survival incidence in Group B versus Group A was 97.5% and 87.2%. Among participants requiring low-flow oxygen with FiO2 < 0.40, cumulative survival incidence was 100% for both groups, but the time of recovery and their discharge were lower in Group B. Among the participants requiring high flow, NIV, or FiO2 > 0.40, cumulative survival incidence was 71.8% and 21.4% for Group B and Group A, respectively [Table 3] and [Table 4].
Table 3: Baseline clinical status at the time of admission

Click here to view
Table 4: Clinical status of study participants by day 7

Click here to view


Data calculated on the day 7 showed that out of 20 (50%) participants of Group B on high flow from the day of admission 11 (55%) were shifted to low-flow supplementation. Whereas in Group A, 4 (26.7%) out of 15 (38.5%) participants showed reduction in oxygen requirement and were shifted to low-flow from high-flow oxygen supplementation and 2 (13.3%) patients were put on NIPPV. In Group B, 1 (8.3%) participant out of 12 (30% on NIPPV since admission), and in Group A, 5 (38.5%) participants out of 13 (33.3% on NIPPV since admission) required mechanical ventilation and ICU admission within the first 7 days. Incidence among participants requiring high flow, NIV, or FiO2 > 0.40, by 7th day, was 56.3% and 22.5% for Group B and Group A, respectively [Table 4].

In the second assessment by day 14, 2 (5.2%) participants required high flow/NIV and 1 (2.6%) participant required mechanical ventilation in Group A, whereas no patient required high flow/NIV/mechanical ventilation in Group B. Among the total study participants, 1 (2.5%) and 5 (12.8%) participants died in 14 days from the day of admission, among Group B and Group A, respectively [Table 5].
Table 5: Clinical status of participants by day 14

Click here to view



   Discussion Top


In the present quasi-experimental study, we evaluated the therapeutic efficacy of dexamethasone in patients with moderate to severe COVID-19. It was observed that the participants requiring NIV, high-flow oxygen, or FiO2 > 0.40 who received dexamethasone had lower risk of in-hospital death and had decreased ICU stay than those who were receiving standard care alone. The requirement of oxygen by 5th day was significantly reduced after receiving dexamethasone for 5 days, and the same endpoint was observed among patients who required low-flow oxygen with FiO2 < 0.40. The oxygen requirement was significantly reduced in Group B (31), as compared to Group A (17) as observed using 6-point ordinal scale.

COVID-19 can progress from mild to severe illness. The initial pathogenic viral response is followed by the host's inflammatory response characterized by an excessive pro-inflammatory cytokine production resulting in immunopathological lung injury, diffuse alveolar damage, and the development of ARDS, which can eventually lead to death.[3],[4] In this context, the use of corticosteroids to quell the cytokine storm and avoid disease progression has been postulated. Most of the initial data based on previous experiences on SARS-associated coronavirus, middle east respiratory syndrome, and other viral pneumonia did not favor steroids use,[5],[6],[7] and some recent reports have shown that corticosteroids can be beneficial and safe for ICU patients with ARDS infected with SARS-CoV-2.[10],[11] In moderate to severe COVID-19 infection, administration of dexamethasone significantly reduced the escalation of symptoms requiring patient to be shifted from ward to ICU, requirement for mechanical ventilation, and mortality. The present study showed that treating the patients with dexamethasone significantly reduced the requirements of the use of external oxygen supply but not among those receiving no respiratory support. It is likely that the benefit of dexamethasone treatment is proportional to the degree of disease severity. Likewise, it seems quite unlikely that all patients will benefit to the same degree from dexamethasone use. For some patients, steroids might even be harmful. Therefore, identification of those patients who could benefit the most from dexamethasone treatment is of great interest and importance. In Group B, with the use of dexamethasone, participants on NIV got shifted to only high-flow oxygen supplementation and maintaining >95% oxygen saturation earlier than Group A. Similarly, those on high-flow oxygen got shifted to low-flow oxygen requirement and maintained desired saturation.

The study presents several limitations owing to the current pandemic situation. The quasi-experimental design prevents randomization of the groups. The study had a short follow-up period of 14 days which may be increased in future studies. The adverse effects of corticosteroid treatment were not recorded during the study.


   Conclusion Top


The results reported here show that among COVID-19 participants receiving oxygen without IMV, corticosteroid treatment was associated with reduced mortality and ICU stay in patients with NIV or high-flow oxygen requirements. These findings can strengthen the treatment protocol designed for COVID-19 patients, especially during this time of global pandemic situation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Team NCPERE. Vital surveillances: The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) – China. China CDC Wkly 2020;2:113-22.  Back to cited text no. 1
    
2.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020;8:475-81.  Back to cited text no. 2
    
3.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020;130:2620-9.  Back to cited text no. 3
    
4.
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020;368:473-4.  Back to cited text no. 4
    
5.
Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med 2018;197:757-67.  Back to cited text no. 5
    
6.
Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, et al. Effects of early corticosteroid treatment on plasma SARS-associated coronavirus RNA concentrations in adult patients. J Clin Virol 2004;31:304-9.  Back to cited text no. 6
    
7.
Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: A systematic review and meta-analysis. Crit Care 2019;23:99.  Back to cited text no. 7
    
8.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704.  Back to cited text no. 8
    
9.
Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, et al. Infectious Diseases Society of America Guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis 2020:ciaa478. Available from: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/. [Last accessed on 2021 Jul 15].  Back to cited text no. 9
    
10.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180:934-43.  Back to cited text no. 10
    
11.
Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, et al. Dexamethasone treatment for the acute respiratory distress syndrome: A multicentre, randomised controlled trial. Lancet Respir Med 2020;8:267-76.  Back to cited text no. 11
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Tables

 Article Access Statistics
    Viewed334    
    Printed4    
    Emailed0    
    PDF Downloaded52    
    Comments [Add]    

Recommend this journal