Skip to main content
Download PDF

Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study

BMC Infectious Diseases volume 24, Article number: 189 (2024) Cite this article

Abstract

Background

Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone’s clinical and safety outcomes compared to methylprednisolone.

Methods

A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient’s age and MODS within 24 h of ICU admission.

Results

After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups.

Conclusion

Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Peer Review reports

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the leading cause of coronavirus disease 2019 (COVID-19) [1]. Around 26–32% of patients with COVID-19 may require intensive care unit (ICU) admission [2, 3]. The mortality rate of critical COVID-19 cases ranges from 26%-48% [4,5,6]. Patients infected with SARS-CoV-2 experience a systemic hyperinflammatory response [7, 8]. This reaction is driven by the high cytokine levels, causing several life-threatening complications such as acute respiratory distress syndrome and multisystem organ failure [7, 8]. The immunomodulatory agents targeting cytokine release and hyperinflammatory response have been a potential treatment option for critically ill patients with COVID-19 [9, 10]. Several immunomodulators agents, such as corticosteroids, interleukin-6 inhibitors (IL-6), and Janus kinase (JAK) inhibitors, have been investigated to treat hospitalized patients with COVID-19 [11,12,13,14].

Corticosteroids have anti-inflammatory and immunosuppressive actions that reduce the production of pro-inflammatory cytokines such as IL-6 [15]. Previous studies have shown improved prognosis and survival rate in patients with moderate to severe COVID-19 using corticosteroids therapy, including dexamethasone, methylprednisolone, and hydrocortisone [10, 14, 16,17,18]. However, the use of hydrocortisone or methylprednisolone in this patients population was not supported by solid evidence [19]. The RECOVERY trial is a randomized control study that included 6425 hospitalized patients with COVID-19. The study found that patients using dexamethasone along with standard therapy had a lower mortality rate at 22.9% compared to patients who received standard treatment alone at 25.7% (rate ratio, 0.83; 95% confidence interval (CI), 0.75 to 0.93; P < 0.001) [19].

Methylprednisolone had greater lung tissue-to plasma penetration in rats when compared to dexamethasone. This effect of methylprednisolone might be beneficial to reduce lung damage and prevent respiratory complications [20]. Studies investigating methylprednisolone in patients with severe COVID-19 showed improved survival [10]. Another randomized controlled trial (RCT), including 68 hospitalized patients admitted to the ICU with COVID-19, compared pulse methylprednisolone to the standard of care. This study found the administration of pulse methylprednisolone at the early phase of illness significantly increased survival compared to standard of care (HR 0.293; 95% CI 0.154–0.556; p < 0.001). The use of methylprednisolone helped improve pulmonary symptoms and inflammatory markers [16].

Both intravenous methylprednisolone and dexamethasone, administered in a 2 mg/kg/day and 6 mg/day dose, respectively, demonstrated similar efficacy in reducing hospital length of stay and oxygen therapy needs in patients with severe viral infection manifestation [21]. In contrast, a small RCT that enrolled 86 critically ill ventilated patients with COVID-19; found that patients receiving methylprednisolone have shorter hospitalization and less dependency on mechanical ventilation (MV) compared to dexamethasone [22]. In non-critically ill COVID-19 patients, pneumonia treated with high-dose methylprednisolone showed lower C-reactive protein (CRP), and D-dimer compared to high-dose dexamethasone [1].

Multiple organ dysfunction score (MODS) is a validated tool that measures the severity of MOD in the intensive care unit. MODS consisted of 24 scores that could be used as a prognostic indicator if calculated at ICU admission or as an outcome once calculated during ICU stay. Higher MODS are indicative of a higher probability of ICU mortality [23]. During the pandemic, severe COVID-19 infection was associated with MOD involving cardiovascular, renal, and pulmonary systems [24]. The involvement of many vital organs in patients with coronavirus infection made the MODS as the most relevant indicator for a patient’s complex condition. National Institutes of Health Guidelines recommended using systemic corticosteroids, including dexamethasone and methylprednisolone for hospitalized patients with COVID-19 on supplementary oxygen [19]. Most previous studies investigated the survival benefits and the need for MV. Corticosteroids reduced the risk of endotracheal intubation as indicative of improved lung function [25]. However, the corticosteroid of choice for better clinical outcomes in critically ill patients with COVID-19 remains undetermined. Thus, we conducted this study to assess the short termclinical and safety outcomes of dexamethasone compared to methylprednisolone in critically ill patients with COVID-19.

Methods

Study design

This research is a component of the Saudi Critical Care Pharmacy Research (SCAPE) platform, which has conducted numerous investigations into the safety and efficacy of diverse treatments and therapies for critically ill patients (Saudi Critical Care Pharmacy Research (SCAPE), 2023). The present study’s design and methodologies draw upon those employed in our previously published research [6]. This is a multicenter retrospective cohort study. It included adult critically ill patients with confirmed COVID-19 admitted to the ICUs between March 01, 2020, and July 31, 2021. COVID-19 was diagnosed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) nasopharyngeal or throat swabs. We categorized the included patients into two groups depending on the type of corticosteroids used within 24 h of ICU admission (Dexamethasone or Methylprednisolone). We followed eligible patients until hospital discharge or death. The King Abdullah International Medical Research Center (KAIMRC) authorized the study in February 2022 (Ref.# NRC22R-074–02). Due to the study’s retrospective observational nature, informed consent from study participants was waived. All methods were performed following relevant guidelines and regulations.

Study participants

All adult patients (age ≥ 18 years) with confirmed COVID-19 admitted to the ICUs during the study period who received either dexamethasone or methylprednisolone were assessed for eligibility. Patients were excluded if they received dexamethasone or methylprednisolone before ICU admission or those who were initiated on corticosteroids more than 24 h after ICU admission. Other exclusion criteria include patients who used corticosteroids as concomitant or sequential therapy, ICU discharge, or death within the first 24 h of ICU admission, and those labeled as “Do-Not-Resuscitate” (Fig. 1).

Fig. 1
figure 1

Eligibility criteria flowchart

Full size image

Study setting

This study was conducted at five hospitals in Saudi Arabia: King Abdulaziz Medical City (Riyadh and Jeddah), King Abdulaziz University Hospital (Jeddah), King Abdullah bin Abdulaziz University Hospital (Riyadh), and King Salman Specialist Hospital (Hail). The selection of these centers was based on the geographic distribution, availability of electronic records, and the center’s willingness to participate in the national project. The primary site for this multicenter study was King Abdulaziz Medical City (KAMC- Riyadh), a tertiary care center.

Data collection

Each patients’ data were collected and managed using Research Electronic Data Capture (REDCap®) software hosted by KAIMRC. We gathered patients’ demographic data, comorbidities, vital signs, laboratory tests, baseline severity scores (i.e., MODS, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA)), renal profile, acute kidney injury, use of prone positioning, MV use and parameters (e.g., PaO2/FiO2 ratio, FiO2 requirement) within 24 h of ICU admission. The Glasgow Coma Score (GCS) was collected in the study, with sedation assessment using the Richmond Agitation-Sedation Scale (RASS) for mechanically ventilated (MV) patients. Conscious level evaluation for non-MV patients or those on non-invasive MV utilized the GCS score. Verbal scores were excluded in invasively intubated and sedated patients due to their inability to vocalize, and assessment focused on eye opening and motor scores, allowing for the computation of the GCS sum score in intubated patients. For noninvasive MV patients, the best GCS was used for conscious level assessment, and for invasive MV patients, GCS scores were measured during sedation vacations, offering a comprehensive understanding of their neurological status. We gathered information on liver function tests (LFTs), coagulation profile (i.e., INR, aPTT, fibrinogen, D-dimer), and inflammatory markers (Ferritin, procalcitonin, and creatine phosphokinase (CPK)) within 24 h of ICU admission. Data on the use of corticosteroids therapy (type, dose, and duration), the timing of corticosteroids initiation, and tocilizumab use were collected for the eligible patients.

Outcomes

The primary outcome was the multiple organ dysfunction on day three of ICU admission. The secondary outcomes were mortality, hospital Length of Stay, ICU Length of Stay, respiratory failure requiring MV, ventilator-free days (VFDs) at 30 days, and ICU-acquired complications (new-onset atrial fibrillation, AKI, liver injury, hospital-acquired infection, pneumonia, and secondary fungal infection). Outcomes definitions are shown in the Additional file 1.

Statistical analysis

We presented continuous vaiables as mean and standard deviation (SD), or median and lower quartile (Q1) and upper quartile (Q3), as appropriate and categorical variables as number (percentage). The normality assumptions were assessed for all numerical variables using a statistical test (i.e., Shapiro–Wilk test) and graphical representation (i.e., histograms and Q-Q plots). Model fit was assessed using the Hosmer–Lemeshow goodness-of-fit test.

Baseline characteristics and outcome variables were compared between the two study groups. We used the Chi-square or Fisher’s exact test for categorical variables. We compared the normally distributed continuous variables using the student t-test and other non-normally distributed continuous variables with the Mann–Whitney U test. Multivariable Cox proportional hazards regression analyses were performed for the 30-day and in-hospital mortality. The proportionality assumption was assessed before fitting the cox model. Visual assessment was performed to evaluate the hypothesis by plotting a log(-log) plot and testing the correlation of scaled Schoenfeld residuals with rank-ordered time.

Multivariable logistic regression analysis and negative binomial regression were used for the other outcomes considered in this study. Regression analysis was done for the study outcomes after considering propensity scores (PS) as covariates in the model. These scores are generated through PS analysis after considering all relevant covariates, which includes patient’s age and MODS within 24 h of ICU admission. The odds ratios (OR), hazard ratio (HR), or estimates with the 95% CI were reported as appropriate. No imputation was made for missing data as the cohort of patients in our study was not derived from random selection.

The Proc PS match procedure (SAS Cary, NC) was used to match patients who received methylprednisolone therapy (active group) to patients who received dexamethasone therapy (control group) (1:3 ratio) based on patient’s age and MODS within 24 h of ICU admission. A greedy nearest neighbor matching method was utilized; one patient who received methylprednisolone therapy (active) paired with three patients who received dexamethasone (control group), which eventually produced the smallest within-pair difference among all available pairs with treated patients. The difference in the logits of the PS for pairs of patients from the two groups was matched if it was less than or equal to 0.5 times the pooled estimate of the standard deviation. We considered a P value of < 0.05 statistically significant and used SAS version 9.4 for all statistical analyses.

Results

Among 1385 patients who were screened during the study period, 526 patients enrolled after applying the study exclusion criteria. Of these patients, 455 were given dexamethasone, while 71 were given methylprednisolone therapy 24 h after ICU admission. After PS matching (1:3), 264 patients were included (66 patients received methylprednisolone, while 198 patients received dexamethasone) according to the selected criteria. The median dose of methylprednisolone and dexamethasone per day was 80 mg (80, 120) and 6 mg (6, 6), respectively. Methylprednisolone was administered for a median duration of six days (4.7, 10) compared with ten days (9, 11) for the dexamethasone group.

Demographic and clinical characteristics

Most of the patients were male (65.8%) in the whole cohort, and the average age was 62.0 ± 15.25 years. Diabetes mellitus (60.0%) was the most common comorbidity, followed by hypertension (56.3%), dyslipidemia (21.9%), and chronic kidney disease (11.2%). There was a statistically significant difference in the baseline characteristics between the two groups before PS matching.

Patients who received dexamethasone have a lower PaO2/FiO2 ratio, higher use of inotropes/vasopressors, and GCS at admission than methylprednisolone. After PS matching based on the patient’s age and MODS within 24 h of ICU admission, most of the baseline demographics and clinical characteristics were well balanced between the two groups, except for the higher total bilirubin, INR, and P/F ratio in the methylprednisolone group. There were no significant differences in severity scores within 24 h of admission (APACHE II, SOFA scores, and MODS) between the two groups, regardless of PS matching. In addition, the proportion of tocilizumab use within 24 h of ICU admission and the concomitant use of nephrotoxic medications during ICU stay were similar between the two groups (Table 1).

Table 1 Summary of demography and baseline characteristics
Full size table

Multiple organ dysfunction (MODS)

Details of the MODS on day three are shown in (Table 2). Best GCS, CVP, heart rate, pressure adjusted heart rate, and PaO2/FiO2 were significantly different between the two groups. The PaO2/FiO2 on day three of ICU admission was higher in the methylprednisolone group than dexamethasone; however, it was higher at baseline (Table 1). In crude analysis, the MODS on day three of ICU was higher in patients who received methylprednisolone when compared to dexamethasone. Similarly, at regression analysis, patients in the methylprednisolone group have a higher MOD score (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03) (Table 3).

Table 2 Details of the multi-organ dysfunction on day 3
Full size table
Table 3 The outcomes of critically ill patients with COVID-19 after propensity score matching
Full size table

Complications during ICU stay

Among the non-MV patients within 24 h of admission, patients who received methylprednisolone have a higher odd of respiratory failure that requires MV; however, it was not statistically significant (OR 1.60, 95% CI 0.53, 4.85; p = 0.41). Patients who received methylprednisolone had a higher odds of infection complications during ICU than dexamethasone; however, didn’t reach a statistically significant difference. Moreover, other complications during the stay, such as new-onset atrial fibrillation, AKI, and liver injury, were similar between the two groups (Fig. 2a, b).

Fig. 2
figure 2

a Complications during ICU stay. b Infection complications during ICUs

Full size image

30-day and in-hospital mortality

The prevalence of 30-day mortality in the crude analysis was 34.8% in the dexamethasone group compared with 41.7% in patients who received methylprednisolone, which was not statistically significant (P = 0.34). Similarly, multivariable time dependent cox proportional hazards regression analysis, revealed a similar 30-day and in-hospital mortality (HR 0.997, 95% CI 0.97, 1.03; p = 0.85 and HR 1.02 95% CI 1.0, 1.04; p = 0.053 respectively) (Table 3).

Ventilator free days and length of stay

The median VFDs was 18.0 (0.0, 27.0) days in the dexamethasone group compared with 14.0 days in patients who received Methylprednisolone (P = 0.48). In addition, the difference was not statistically significant at regression analysis (beta coefficient: -0.12 (95% CI -0.62, 0.39); P = 0.65). Moreover, there was no statistically significant differences in the ICU and hospital length of stay (beta coefficient: 0.06 (95% CI -0.14, 0.25); P = 0.56 and beta coefficient: -0.15 (95% CI -0.35, 0.05); P = 0.14, respectively) (Table 3).

Discussion

This retrospective multicenter study compared clinical and safety outcomes between dexamethasone and methylprednisolone among 264 critically ill patients with COVID-19. After PS matching and linear regression model analysis, we found a statistically significant lower MODS among patients treated with dexamethasone compared to methylprednisolone. Similar findings were reported after adjusting for age and MODS within 24 h of ICU admission. Indeed, our study found that patients treated with methylprednisolone had significantly lower GCS, higher PaO2/FiO2, and pressure-adjusted heart rate. One possible explanation for higher PaO2/FiO2 is the well-established higher lung tissue-to-plasma ratio of methylprednisolone [26,27,28]. Although is it controversial, it has been considered that dexamethasone penetrates the blood–brain barrier relatively more than other corticosteroids [29,30,31]. This could explain the significantly higher GCS scores among patients treated with dexamethasone in our study. It is important to note that GCS assessment in invasive MV is limited by the uncertainty surrounding GCS assessments in the context of intubation. The CoDEX trial investigated the effect of dexamethasone on COVID-19 patients and concluded that dexamethasone resulted in a significantly higher number of free-from MV days than the standard of care alone despite the similar PaO2/FiO2 ratios of both groups [32]. Furthermore, in the RECOVERY trial, dexamethasone-treated patients had a lower need for renal-replacement therapy and invasive MV [16]. Despite using a lower dexamethasone dose compared to CoDEX trial and having a higher CRP and lower PaO2/FiO2 ratio at admission, our dexamethasone-treated patients had lower MODS [32].

Regarding secondary outcomes in our study, our study showed a higher odds of infection complications during ICU among methylprednisolone-treated cohort than dexamethasone; however, didn’t reach to a statically significant difference. A large meta-analysis suggests higher secondary infections following corticosteroid use among influenza patients [33]. However, similar findings were not observed in other studies that mainly looked at COVID-19 patients [34]. The Metcovid trial included suspected and confirmed cases of COVID-19 and investigated the effect of methylprednisolone on mortality [35]. The similar rates of hospital-acquired infection in the Metcovid study could be explained by the absence of use of other immunomodulator COVID-19 therapies. In our study, a major factor could have contributed to the higher hospital-acquired infection rate with methylprednisolone. Methylprednisolone is a relatively more potent immunosuppressant than dexamethasone [35]. Although it was statistically non-significant, patients treated with methylprednisolone had higher ICU and hospital lengths of stay. Several studies showed longer hospital and ICU lengths of stay result in a higher infection rate [36, 37].

Most importantly, the higher MODS and infection rates were not translated into a higher mortality rate with methylprednisolone than dexamethasone. While we did not statistically adjust for SOFA scores or age, the relatively young patient population and low predicted mortality rate based on SOFA scores among our patients could have impacted the mortality rates in our analysis. Similarly, other studies demonstrated a reduction in 28-days and in-hospital mortality [10, 12,13,14]. Three of the studies mentioned included more elderly patients and had used more immunomodulators [10, 12, 13]. Another study included patients with much lower CRP than ours, indicating a less acute COVID-19 inflammation [14]. These factors could be attributed to the lower mortality rates in other studies. In contrast to other studies, we reported similar outcomes between methylprednisolone and dexamethasone on ventilator-free days and respiratory failure requiring MV [10, 12, 34]. The low need for MV at admission and lower ICU admission rates in the previously published studies might explain the differences in our findings.

Our study has a few limitations, including its retrospective nature which limit capturing some important variables such a; medications used prior to ICU admission, as well as onset of complications such as infections and relatively small sample size. In addition, our primary outcome MODS was only assessed at day three which limits the evaluation of the variation in MODS scores between the two groups over a continuous period. On the other hand, this study has some strengths, including multicenter patient recruitment, and PS matching was used to eliminate a greater portion of bias and create a balanced dataset.

Conclusion

This study showed a lower MODS on day three of ICU admission in critically ill patients with COVID-19 treated with dexamethasone. However, both interventions had a similar mortality rate. Future RCTs are needed to confirm our findings and to assess MODS over an extended period during ICU stay.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Pinzón MA, Ortiz S, Holguín H, Betancur JF, Cardona Arango D, Laniado H, et al. Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia. PLoS One. 2021;16:e0252057.

    Article  PubMed  PubMed Central  Google Scholar 

  2. González J, Benítez ID, Carmona P, Santisteve S, Monge A, Moncusí-Moix A, et al. Pulmonary function and radiologic features in survivors of critical COVID-19: a 3-month prospective cohort. Chest. 2021;160:187–98.

    Article  PubMed  Google Scholar 

  3. Abate SM, Ahmed Ali S, Mantfardo B, Basu B. Rate of intensive care unit admission and outcomes among patients with coronavirus: a systematic review and meta-analysis. PLoS One. 2020;15:e0235653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Carbonell R, Urgelés S, Rodríguez A, Bodí M, Martín-Loeches I, Solé-Violán J, et al. Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU: a multicentre retrospective cohort study. Lancet Reg Heal Eur. 2021;11:100243.

    Article  Google Scholar 

  5. Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med. 2020;180:1345–55.

    Article  CAS  PubMed  Google Scholar 

  6. Al Sulaiman KA, Aljuhani O, Eljaaly K, Alharbi AA, Al Shabasy AM, Alsaeedi AS, et al. Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): a multicenter cohort study. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2021;105:180–7.

    CAS  Google Scholar 

  7. Samudrala PK, Kumar P, Choudhary K, Thakur N, Wadekar GS, Dayaramani R, et al. Virology, pathogenesis, diagnosis and in-line treatment of COVID-19. Eur J Pharmacol. 2020;883:173375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020;395:497–506.

    Article  CAS  PubMed  Google Scholar 

  9. Singh AK, Majumdar S, Singh R, Misra A. Role of corticosteroid in the management of COVID-19: a systemic review and a clinician’s perspective. Diabetes Metab Syndr. 2020;14:971–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alunno A, Najm A, Mariette X, De Marco G, Emmel J, Mason L, et al. Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider. Ann Rheum Dis. 2021;80:803–15.

    Article  CAS  PubMed  Google Scholar 

  11. Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, Arabi YM, et al. Interleukin-6 receptor antagonists in critically Ill patients with Covid-19. N Engl J Med. 2021;384:1491–502.

    Article  PubMed  Google Scholar 

  12. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-45. https://doi.org/10.1016/S0140-6736(21)00676-0.

  13. Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus Remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384:795–807.

    Article  CAS  PubMed  Google Scholar 

  14. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384:693–704.

    Article  CAS  PubMed  Google Scholar 

  15. Khiali S, Entezari-Maleki T. Therapeutic application of corticosteroids in COVID-19: a focus on optimum dose and duration of therapy. J Clin Pharmacol. 2021;61:1145–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Edalatifard M, Akhtari M, Salehi M, Naderi Z, Jamshidi A, Mostafaei S, et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020;56:2002808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA. 2020;324:1317–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fadel R, Morrison AR, Vahia A, Smith ZR, Chaudhry Z, Bhargava P, et al. Early short-course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis an Off Publ Infect Dis Soc Am. 2020;71:2114–20.

    Article  CAS  Google Scholar 

  19. RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693-704. https://doi.org/10.1056/NEJMoa2021436.

  20. Ayyar VS, Song D, DuBois DC, Almon RR, Jusko WJ. Modeling corticosteroid pharmacokinetics and pharmacodynamics, part I: determination and prediction of dexamethasone and methylprednisolone tissue binding in the rat. J Pharmacol Exp Ther. 2019;370:318–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mehta J, Rolta R, Mehta BB, Kaushik N, Choi EH, Kaushik NK. Role of dexamethasone and methylprednisolone corticosteroids in coronavirus disease 2019 hospitalized patients: a review. Front Microbiol. 2022;13:813358.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021;21:337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23:1638–52.

    Article  CAS  PubMed  Google Scholar 

  24. Wu T, Zuo Z, Kang S, Jiang L, Luo X, Xia Z, et al. Multi-organ dysfunction in patients with COVID-19: a systematic review and meta-analysis. Aging Dis. 2020;11:874–94.

    Article  PubMed  PubMed Central  Google Scholar 

  25. EbrahimiChaharom F, Pourafkari L, EbrahimiChaharom AA, Nader ND. Effects of corticosteroids on Covid-19 patients: a systematic review and meta-analysis on clinical outcomes. Pulm Pharmacol Ther. 2022;72:102107.

    Article  CAS  Google Scholar 

  26. Papamanoli A, Yoo J, Grewal P, Predun W, Hotelling J, Jacob R, et al. High-dose methylprednisolone in nonintubated patients with severe COVID-19 pneumonia. Eur J Clin Invest. 2021;51:e13458.

    Article  CAS  PubMed  Google Scholar 

  27. Hui DSC, Sung JJY. Severe acute respiratory syndrome. Chest. 2003;124:12–5.

    Article  PubMed  Google Scholar 

  28. Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A, Briegel J, et al. Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med. 2017;43:1781–92.

    Article  PubMed  Google Scholar 

  29. Karssen AM, Meijer OC, de Kloet ER. Chapter 3.4 Corticosteroids and the blood-brain barrier. Tech Behav Neural Sci. 2005;15 PART 1:329–40.

    Article  Google Scholar 

  30. Hurwitz CA, Silverman LB, Schorin MA, Clavell LA, Dalton VK, Glick KM, et al. Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia. Cancer. 2000;88:1964–9. https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/(SICI)1097-0142(20000415)88:8%3C1964::AID-CNCR27%3E3.0.CO;2-1. Accessed 3 Oct 2022.

    Article  CAS  PubMed  Google Scholar 

  31. Balis FM, Lester CM, Chrousos GP, Heideman RL, Poplack DG. Differences in cerebrospinal fluid penetration of corticosteroids: possible relationship to the prevention of meningeal leukemia. J Clin Oncol. 1987;5:202–7.

    Article  CAS  PubMed  Google Scholar 

  32. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324:1307–16.

    Article  CAS  PubMed  Google Scholar 

  33. Ni Y-N, Chen G, Sun J, Liang B-M, Liang Z-A. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019;23:99.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with coronavirus disease 2019 (COVID-19; Metcovid): a randomized, double-blind, phase IIb, placebo-controlled trial. Clin Infect Dis an Off Publ Infect Dis Soc Am. 2021;72:e373–81.

    Article  CAS  Google Scholar 

  35. Langhoff E, Ladefoged J. Relative immunosuppressive potency of various corticosteroids measured in vitro. Eur J Clin Pharmacol. 1983;25:459–62.

    Article  CAS  PubMed  Google Scholar 

  36. Hassan M, Tuckman HP, Patrick RH, Kountz DS, Kohn JL. Hospital length of stay and probability of acquiring infection. Int J Pharm Healthc Mark. 2010;4:324–38.

    Article  Google Scholar 

  37. Jia H, Li L, Li W, Hou T, Ma H, Yang Y, et al. Impact of healthcare-associated infections on length of stay: a study in 68 hospitals in China. Biomed Res Int. 2019;2019:2590563.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all the investigators who participated in this project from the Saudi critical care pharmacy research (SCAPE) platform.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

    Ohoud Aljuhani & Daniah AlMohammady

  2. Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

    Ghazwa B. Korayem & Amjaad Alfahed

  3. Pharmaceutical Care Services, King Salman Specialist Hospital, Hail Health Cluster, Ministry of Health, Hail, Saudi Arabia

    Ali F. Altebainawi

  4. Department of Medicine, King Khalid Hospital, Hail Health Cluster, Hail, Saudi Arabia

    Elaf F. Altebainawi

  5. Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia

    Hisham A. Badreldin, Rahaf Ali Alqahtani, Fahad Al Dhahri, Shmeylan Al Harbi & Khalid Al Sulaiman

  6. College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Hisham A. Badreldin, Fahad Al Dhahri, Shmeylan Al Harbi & Khalid Al Sulaiman

  7. King Abdullah International Medical Research Center-King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard – Health Affairs, Riyadh, Saudi Arabia

    Hisham A. Badreldin, Fahad Al Dhahri, Shmeylan Al Harbi, Raed Kensara & Khalid Al Sulaiman

  8. Norwich clinical trial unit, Norwich medical school, University of east Anglia, Norwich, UK

    Ramesh Vishwakarma

  9. Clinical Pharmacy Department, Pharmacy Services Administration, King Fahad Medical City, Riyadh, Saudi Arabia

    Faisal E. Almutairi

  10. Pharmaceutical Care Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia

    Abeer A. Alenazi

  11. Family Medicine Department, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

    Thamer Alsulaiman

  12. Pharmaceutical Care Services, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia

    Namareq Aldardeer

  13. Pharmaceutical Care Department, King Abdulaziz Medical City, Dammam, Saudi Arabia

    Ahmed O. Alenazi

  14. Pharmaceutical Care Department, King Abdulaziz Medical City, Jeddah, Saudi Arabia

    Raed Kensara

  15. Pharmaceutical Care Services, King Abdulaziz Medical City, Jeddah, Saudi Arabia

    Mai Alalawi

  16. Clinical and Administrative Pharmacy Sciences, College of Pharmacy, Howard University, Washington, DC, 20059, USA

    Mohammed Aldhaeefi

  17. Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Saudi Arabia

    Ali F. Altebainawi

  18. King Abdulaziz Medical City (KAMC) - Ministry of National Guard Health Affairs (MNGHA), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, PO Box 22490, Riyadh, 11426, Saudi Arabia

    Khalid Al Sulaiman

Authors
  1. Ohoud Aljuhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ghazwa B. Korayem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ali F. Altebainawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniah AlMohammady
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amjaad Alfahed
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elaf F. Altebainawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammed Aldhaeefi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hisham A. Badreldin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ramesh Vishwakarma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Faisal E. Almutairi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Abeer A. Alenazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Thamer Alsulaiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rahaf Ali Alqahtani
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Fahad Al Dhahri
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Namareq Aldardeer
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ahmed O. Alenazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Shmeylan Al Harbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Raed Kensara
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Mai Alalawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Khalid Al Sulaiman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made a significant contribution to the work reported. The contribution was on either the study conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas. Some authors contributed to drafting, revising, or critically reviewing the article, giving final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Khalid Al Sulaiman.

Ethics declarations

Ethics approval and consent to participate

The study was approved in February 2022 by the primary center King Abdullah International Medical Research Center Institutional Review Board, Riyadh, Saudi Arabia (Ref.# NRC22R-074-02). In addition, ethical approvals were obtained from each participant center. Participants’ confidentiality was strictly observed throughout the study, using the anonymous unique serial number for each subject, and restricting data only to the investigators. King Abdullah International Medical Research Center Institutional Review Board waived the informed consent due to the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

Outcome definition (s).

Rights and permissions

Open Access This 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.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aljuhani, O., Korayem, G.B., Altebainawi, A.F. et al. Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study. BMC Infect Dis 24, 189 (2024). https://doi.org/10.1186/s12879-024-09056-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-024-09056-y

Keywords

BMC Infectious Diseases

ISSN: 1471-2334

Contact us