Is there any literature to support dexamethasone use in COPD exacerbation? What dose is recommended if so?

Comment by InpharmD Researcher

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines suggest systemic glucocorticoids in COPD exacerbation may improve outcomes, including recovery time, lung function, and oxygenation. A limited number of studies have investigated the use of IV dexamethasone for COPD exacerbations. Results from these studies vary. Some data demonstrated comparable efficacy between dexamethasone and methylprednisolone, while others showed significantly greater improvement with methylprednisolone. A 40 mg of prednisone-equivalent daily for 5 days is recommended in GOLD, with individual studies varying in dose strategies (2 mg/kg or 8 mg).

Background

Per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD), updated in 2023, oral glucocorticoids are considered equally effective as intravenous (IV) administration. Studies, mostly set in hospitals, suggest systemic glucocorticoids in COPD exacerbations can shorten recovery time, improve lung function and oxygenation, reduce the risk of early relapse and treatment failure, and decrease hospital length of stay (LOS). The recommended systemic corticosteroid dose is 40 mg of prednisone-equivalent daily for 5 days. Longer courses of oral corticosteroids were associated with an increased risk of pneumonia and mortality in one observational study. Even short courses of corticosteroids were associated with an increased risk of pneumonia, sepsis, and death. If a steroid-sparing regimen is needed, one study found that nebulized budesonide alone provides similar benefits to IV methylprednisolone. The only time systemic dexamethasone, specifically, is mentioned in these updated guidelines is in the context of hospitalized patients with COVID-19. [1]

In addition to two relevant randomized trials (Tables 1 and 2), a 2021 prospective study, published as a poster abstract, investigated the use of IV dexamethasone for hyperinflammatory cardiopulmonary exacerbations in very elderly patients with acute heart failure (HF) and concomitant acute lung diseases characterized by inflammation. The study enrolled 157 patients aged ≥80 years with acute HF and symptoms attributable to acute bronchitis, pneumonia, or exacerbated COPD. Patients also had N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels ≥ 3,000 pg/mL and radiographic evidence of pulmonary congestion with or without lung consolidation; patients with COVID-19 were excluded from the study. A total of 96 patients with C-reactive protein (CRP) values > 20 mg/dL were randomized into two groups: 48 patients were treated with open-label IV dexamethasone 8 mg/day in addition to usual therapies, and 48 received usual therapy alone. Patients were assessed for clinical recovery time, duration of hospitalization, in-hospital mortality, need for re-hospitalization, and mortality at one month. The dexamethasone group showed faster clinical recovery and shorter hospital stays, but no significant differences were seen for in-hospital mortality, 30-day mortality, or re-hospitalization rates compared to the usual therapy group. Although this study suggests a favorable response to dexamethasone in terms of clinical recovery and hospitalization length, the authors note that further evaluation through larger, double-blind, randomized trials is necessary to assess dexamethasone’s potential impact on mortality improvement. [2]

A 2021 single-blind, randomized clinical trial evaluated the comparative efficacy of IV dexamethasone (8 mg daily) and hydrocortisone (200 mg daily in divided doses) in the management of COPD exacerbations. The trial enrolled 70 patients aged over 40 with confirmed COPD, randomly assigned into two treatment groups. The interventions were assessed on their impact on clinical symptoms, including shortness of breath, sputum volume and viscosity, cough, oxygen saturation, peak expiratory flow (PEF), and biomarkers of inflammation and oxidative stress such as C-reactive protein (CRP) and malondialdehyde (MDA). Outcomes were measured at baseline, day two, and discharge, and side effects, such as edema and blood pressure changes, were monitored systematically. Both dexamethasone and hydrocortisone demonstrated equivalent improvements in clinical indicators, with significant symptom alleviation observed within each group (p<0.001). However, intergroup analyses revealed statistically significant differences on the first day for shortness of breath, sputum volume, and arterial oxygen saturation (p= 0.02, p= 0.01, p= 0.02, respectively). These differences equalized by discharge, suggesting comparable long-term efficacy. Inflammatory markers, including CRP and WBC counts and MDA levels, showed significant reductions in both cohorts without meaningful differences between the groups. Notably, hydrocortisone was associated with a higher incidence of edema (17% vs. 5.7%, p= 0.009), likely attributable to its mineralocorticoid activity. These findings underscore the therapeutic equivalence of dexamethasone and hydrocortisone in COPD exacerbations, with dexamethasone offering a potential advantage for patients susceptible to fluid retention. [3]

A 2023 retrospective, cross-sectional, comparative study evaluated the effects of pre-hospital dexamethasone administration on outcomes in patients experiencing exacerbations of asthma and COPD. The analysis utilized emergency medical service (EMS) patient care reports and emergency department (ED) records from January 2021 to October 2022, focusing on 200 patients (93 with COPD and 107 with asthma) who were either treated or not treated with dexamethasone in the pre-hospital setting. Key parameters examined included ED-LOS and hospital admission rates. Patients in the dexamethasone-treated group received 8 mg intravenously administered by paramedics or emergency nurse practitioners at the scene, based on nationally established EMS protocols. The findings demonstrated that pre-hospital dexamethasone administration was associated with a significant reduction in ED-LOS among asthma exacerbation cases, with median times of 235 minutes versus 322 minutes when compared to the untreated group (p= 0.003). However, while hospital admission rates for asthma patients trended lower in the dexamethasone-treated group (60.4% vs. 78.0%), the difference was not statistically significant (p= 0.510). Among COPD patients, dexamethasone use was associated with a non-significant reduction in ED-LOS (232 vs. 296 minutes, p= 0.106) and hospital admission rates (80.8% vs. 85.4%, p= 0.561). These results emphasize the potential benefits of pre-hospital dexamethasone in reducing ED-LOS in asthma exacerbations, though its impact on hospital admission rates and outcomes in COPD remains less definitive. [4]

References: [1] Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of COPD 2023 Report. https://goldcopd.org/2023-gold-report-2/
[2] Cosmi D, Mariottoni B, Angori P, et al. C82 Dexamethasone in acute cardiopulmonary syndrome with hyperinflammatory state. European Heart Journal Supplements. 2021;23(Supplement_C):C1-C48. doi:10.1093/eurheartj/suab063
[3] Hosseini A, Doustimotlagh AH, Afrasiabifar A, Sedaghattalab S. Comparison of dexamethasone and hydrocortisone in management of exacerbated chronic obstructive pulmonary disease patients; a randomized controlled trial. Journal of Clinical Care and Skills. 2023;4(2):63-69.
[4] Huabbangyang T, Silakoon A, Sangketchon C, et al. Effects of Pre-Hospital Dexamethasone Administration on Outcomes of Patients with COPD and Asthma Exacerbation; a Cross-Sectional Study. Arch Acad Emerg Med. 2023;11(1):e56. Published 2023 Aug 12. doi:10.22037/aaem.v11i1.2037
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any literature to support dexamethasone use in COPD exacerbation? What dose is recommended if so?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→



Please see Tables 1-2 for your response.


 

Methyl prednisolone vs Dexamethasone in Management of COPD Exacerbation; a Randomized Clinical Trial

Design

Randomized, single-center, single-blind trial

N= 68

Objective

To compare the efficacy of methylprednisolone and dexamethasone in the treatment of chronic obstructive pulmonary disease (COPD) exacerbation

Study Groups

Methylprednisolone (n= 34)

Dexamethasone (n= 34)

Inclusion Criteria

Adults, COPD diagnosis with exacerbation present (acute respiratory distress, increased cough frequency and severity, increased sputum volume, and/or increased wheezing ≥ 24 hours)

Exclusion Criteria

Steroid use in the month prior to presentation; history of asthma or atopy; onset of respiratory distress before 35 years of age; absence of spirometric data

Methods

Patients admitted to an emergency department in Iran were randomized to either methylprednisolone or dexamethasone. The methylprednisolone group received 2 mg/kg/day intravenously (IV) for three days, before a reduction in dose to 40 mg/day for three days, then 30 mg/day for three days, then subsequently tapered down by 5 mg every three days. Inhaled budesonide was prescribed for three months of continuous use afterward, alongside a taper of prednisone for two weeks.

The dexamethasone arm received 0.375 mg/kg/day IV, then was gradually tapered. After 7 to 14 days, dexamethasone was replaced by 30 mg/day of methylprednisolone, and then followed the tapering schedule and succeeding steroid protocol the methylprednisolone arm was subject to.

Duration

2013 to 2014

Follow-up: Two weeks

Outcome Measures

Improvement in sputum volume, sputum viscosity, dyspnea, cough; O2, PaCO2, HCO3, serum pH, white blood cell (WBC) counts

Baseline Characteristics

 

Dexamethasone (n= 34)

Methylprednisolone (n= 34)

 

Age, years

74.67 ± 1.79 73.35 ± 2.25  

Male

82.3% 82.4%  

Duration of disease, years

8.02 ± 5.25 8.64 ± 4.61  

Shortness of breath

None

Mild

Moderate

Severe

 

11.8%

8.8%

20.6%

58.8%

 

0

17.6%

23.5%

58.8%

 

Cough

None

Mild

Moderate

Severe

 

11.8%

5.9%

26.5%

55.9%

 

0

8.8%

32.4%

58.8%

 

Sputum volume

None

Mild

Moderate

Severe

 

23.5%

14.7%

14.7%

47.1%

 

0

23.5%

14.7%

61.8%

 

High sputum viscosity present

52.9%

61.8%

 

O2 saturation on arrival, %

PaCO2 on arrival, mmHg

HCO3 on arrival, mEq/L

Serum pH on arrival

79.26 ± 6.61

64.85 ± 10.00

26.55 ± 5.37

7.32 ± 0.04

78.65 ± 8.24

64.85 ± 12.52

27.76 ± 5.52

7.30 ± 0.05

 

WBC count/mm3 before treatment

8.49 ± 3.6

7.35 ± 3.08

 

Results

 

Dexamethasone (n= 34)

Methylprednisolone (n= 34)

p-value

Improvement in sputum volume by day 14

84.85% 82.35% 0.05

Improvement in sputum viscosity by day 14

72.72% 100.0% 0.24

Improvement in dyspnea by day 14

90.91% 94.12% 0.02

Improvement in cough by day 14

75.76% 79.41% 0.035

O2 saturation, %

90.97 ± 3.31 92.52 ± 2.74 0.87

PaCO2, mmHg

44.32 ± 3.35 45.32 ± 3.91 0.83

HCO3, mEq/L

23.12 ± 2.17 23.91 ± 2.23 0.12

Serum pH

7.36 ± 0.05 7.36 ± 0.03 0.42

WBC count/mm3

6.81 ± 1.92 6.80 ± 1.95 0.24

Adverse Events

Gastrointestinal bleeding

9.1% 14.7% 0.71

Mood change

0 8.8% 0.24

Heartburn

27.3% 17.6% 0.39

Blood sugar disturbance

27.3% 17.6% 0.39

Study Author Conclusions

Methylprednisolone and dexamethasone have similar efficacy and side effects in treatment of patients with COPD exacerbation, and selecting drug of choice would better be based on the most prominent symptoms of patients.

InpharmD Researcher Critique

Although randomized, this study had a small sample size and was single-blinded. Improvement in symptoms by day 14 was scored by patients on a scale of 0 (much better than usual) to 5 (much worse than usual), potentially distorting the treatment effect. There may also be a potential crossover effect since dexamethasone patients were switched to methylprednisolone at the time of the final evaluation at 14 days. Additionally, due to short follow-up, potential secondary exacerbations are unaccounted for.



References:
[1] Emami Ardestani M, Kalantary E, Samaiy V, Taherian K. Methyl prednisolone vs Dexamethasone in Management of COPD Exacerbation; a Randomized Clinical Trial. Emerg (Tehran). 2017;5(1):e35.

 

A step-wise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of COPD

Design

Randomized, single-center, single-blind trial

N= 142

Objective

To compare the effects of methylprednisolone with those of dexamethasone in acute exacerbations of chronic obstructive pulmonary disease (COPD), and to confirm which is the better treatment

Study Groups

Methylprednisolone (n= 71)

Dexamethasone (n= 71)

Inclusion Criteria

Adults, COPD diagnosis with exacerbation present (acute respiratory distress, increased cough frequency and severity, increased sputum volume, and/or increased wheezing ≥ 24 hours), history of emphysema or chronic bronchitis

Exclusion Criteria

Steroid use in the month prior to presentation; history of asthma or atopy; onset of respiratory distress before 35 years of age; absence of spirometric data; invasive mechanical ventilation by tracheal intubation; any other condition resulting in hospital admission

Methods

Patients admitted to a single Chinese hospital were randomized to either methylprednisolone or dexamethasone. The methylprednisolone arm received 2 mg/kg/day intravenously (IV) for three days, before a reduction in dose by 40 mg, then subsequently reduced every three days. Around 7 to 14 days, patients were switched to 30 mg/day of oral prednisone, reduced by 5 mg every 3 days until they were taking 5 mg/day. Inhaled budesonide was prescribed for three months of continuous use afterward alongside the prednisone taper for two additional weeks.

The dexamethasone arm received 0.375 mg/kg/day IV, then gradually tapered. After 7 to 14 days, dexamethasone was replaced by 30 mg/day of prednisolone, and then followed the tapering schedule and succeeding steroid protocol the methylprednisolone arm was subject to.

Duration

1998 to 2002

Follow-up: 7 days

Outcome Measures

Symptom score, forced expiratory volume (FEV1), blood gases, white blood cells (WBC) count, chest radiography, and pathology tests

Baseline Characteristics

 

Methylprednisolone (n= 71)

Dexamethasone (n= 71)

 

Age, years

55.60 ± 12.50 60.40 ± 9.20  

Duration of disease, years

25.90 ± 12.40 26.60 ± 11.80  

Symptom score*

26.10 ± 5.40 25.80 ± 5.70  

PaO2 pretreatment, kpa

PaCO2 pretreatment, kpa

SaO2 pretreatment, %

FEV1 pretreatment, %

7.40 ± 2.50

5.60 ± 1.47

85.20 ± 12.70

47.70 ± 10.60

8.90 ± 2.10

5.14 ± 1.26

85.20 ± 12.70

50.10 ± 7.60

 

Pneumonia

Unilateral

Bilateral

 

17%

35%

 

14%

30%

 

WBC count pretreatment, x109/L

12.74 ± 2.05

9.69 ± 4.11

 

Neutrophils, %

79.63 ± 10.11

77.47 ± 8.21

 

*Symptom score was calculated from a diary completed by the patient, scoring their symptoms from 0 (much better than usual) to 5 (much worse than usual)

WBC in the methylprednisolone arm was higher than the dexamethasone arm prior to therapy initiation (p= 0.045).

Results

 

Methylprednisolone (n= 71)

Dexamethasone (n= 71)

p-value

Symptom score on day 7

15.4 ± 5.2 21.6 ± 3.7 0.045

Predicted FEV1 on day 7, %

67.5 ± 12.4  58.9 ± 10.8 0.048

PaO2 on day 7, kpa

10.88 ± 0.66 9.4 ± 1.05 0.185

PaCO2 on day 7, kpa

5.58 ± 0.37 5.16 ± 0.54 0.332

SaO2 on day 7, %

95.58 ± 0.94 93.62 ± 2.67 0.045

WBC count on day 7, x109/L

9.57 ± 3.85 9.35 ± 2.67 0.626

Neutrophils on day 7, %

78.23 ± 8.76 76.82 ± 6.02 0.624

Adverse Events

Several patients were reported to have blood sugar elevation that resolved once steroid dose was reduced. One patient presented with a pneumothorax during treatment, which was then resolved. No patients died during hospitalization. Specific incidences were not reported.

Study Author Conclusions

An adequate and tapering dose of methylprednisolone used in acute exacerbations of COPD can relieve the inflammatory reaction in airways and reduce airway spasm more promptly than dexamethasone.

InpharmD Researcher Critique

Treatment arms that patients with adverse events belonged to, as well as total number of patients who experienced adverse events, were not reported. A short follow-up period also makes it difficult to determine if either corticosteroid successfully resolved the exacerbations. Additional limitations include the open-label, single-center design in a Chinese population. 



References:
[1] Li H, He G, Chu H, Zhao L, Yu H. A step-wise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of COPD. Respirology. 2003;8(2):199-204. doi:10.1046/j.1440-1843.2003.00468.x