Corticosteroids in ARDS
Abstract
:1. Introduction
1.1. Sepsis—Definition, Epidemiology and Pathophysiology
1.2. Acute Respiratory Distress Syndrome [ARDS]—Definition, Epidemiology and Pathophysiology
1.3. Corticosteroids
2. Corticosteroids in ARDS
2.1. Corticosteroids in Early Stage ARDS [Table 1]
2.2. Corticosteroids in Late-Stage ARDS
2.3. Dose and Type of Corticosteroid
2.4. Pathogens
2.5. Adverse Events
Author, Reference | Type | Sample Size | Study Population | Treatment | Results |
---|---|---|---|---|---|
Bernard et al. [63] | RCT, multicenter | 99 | ARDS as Partial pressure of oxygen ≤ 70 mm Hg on > 40% oxygen, PaO2/PAO2 ratio < 0.3, bilateral lung infiltrates, pulmonary artery wedge pressure ≤ 18 mm Hg | MPS 30 mg/kg IV 6 hourly for 24 h vs. placebo | PEP mortality MPS 30/50 (60%); Pl 31/49 (63.2) OR 0.75 [0.4 to 1.57] p = 0.74 |
Meduri et al. [60] | RCT multicenter | 24 | ARDS 1994 7 days of mechanical ventilation with an LIS of 2.5 or greater and less than a 1-point reduction from day 1 of ARDS, and no evidence of untreated infection. | MPS Loading dose of 2 mg/kg; then 2 mg/kg/d from day 1 to day 14, 1 mg/kg/d from day 15 to day 21, 0.5 mg/kg/d from day 22 to day 28, 0.25 mg/kg/d on days 29 and 30, 0.125 mg/kg/d on days 31 and 32. vs. placebo | PEP Lung injury and mortality day 10 MPS 1.7 [0.1]; Pl 3.0 [0.2]; p < 0.001 SEP: Mortality MPS 0/16 (0%); Pl 5/8 (62%) p = 0.002 Mortality in hospital MPS 2/16 (12.5%); Pl 5/8 (62.5%) OR 0.41 [0.06 to 99] p = 0.03 |
Steinberg et al., ARDSnetwork, [67] | RCT Multicenter | 132/180 | ARDS 1994 in early and late stage At least 7 days duration ARDS; p/F < 200 Intubated, mechanical ventilation | MPS Loading dose of 2 mg/kg of predicted body weight followed by 0.5 mg/kg 6 hourly for 14 days; 0.5 mg/kg 12 hourly for 7 days; and then tapering of the dose. | In early ARDS (7–13 d) PEP mortality at 60 days MPS (36%); Pl (27%) p = 0.26 |
Annane et al. [47] | post Hoc RCT | 129/300 177 ARDS: 129 non responders, 48 responder | ARDS 1994 bilateral infiltrate on chest radiography, PaO2/FiO2 < 200 mm Hg and Pulmonary occlusion pressure ≤ 18 mm Hg or no clinical evidence of left atrial hypertension | HSHC 50 mg IV 6 hourly and 9-alpha fludrocortisone once a day for 7 days. | PEP: mortality at 28-day In the non-responder subgroup HSHC + FC 33/62 (53%); Pl 50/67 (75%) RR = 0.71; 95% CI [0.54 to 0.94] p = 0.013 OR = 0.35; 95% CI [0.15 to 0.82], p = 0.016). In the responder group No significant result HSHC + FC 16/23 (70%); PL 12/25 (48%) RR = 1.4; 95% CI [0.89 to 2.36] p = 0.130 OR = 2.29; 95% CI [0.49 to 10.64] p = 0.290 |
Meduri et al. [61] | RCT multicenter | 91 | ARDS 1994 Intubated and Mechanical ventilation ARDS ≤ 72 H of study entry | MPS Loading dose of 1 mg/kg Then 1 mg/kg/d from day 1 to day 14, 0.5 mg/kg/d from day 15 to day 21, 0.25 mg/kg/d from day 22 to day 25, 0.125 mg/kg/d from day 26 to day 28. | PEP 1-point reduction in LIS or MPS 69.8% vs. Pl 35.7%; p = 0.002 successful extubation 7-day MPS 53.9% vs. Pl 25.0%; p = 0.01 |
Tongyoo et al. [91] | RCT Single center | 197 | Severe sepsis or septic shock receiving IMV for hypoxemic respiratory failure within 12 H of study entry + ARDS 1994 then reclassified accordingly to ARDS 2012 | HSHC 50 mg every 6 h or placebo | PEP 28 day all-cause mortality HSHC (22.5%) vs. Pl (27.3%) RR 0.82 [0.50 to 1.34] p = 0.51 HR 0.80, 95% CI [0.46 to 1.41]; p = 0.44 |
Villar et al., DEXA-ARDS, [64] | RCT multicenter | 277/314 stopped low enrollment 88% | ARDS 2012 (but PEEP ≥ 10) Moderate to severe ARDS < 24 h (but PEEP ≥ 10) | DXM IV 20 mg once daily day 1 to 5 then 10 mg once daily day 6 to 10 | PEP N° ventilator-free from day of randomization to day 28 Between-group difference 4.8 days 95% CI [2.57 to 7.03]; p < 0.0001). |
Horby et al., RECOVERY, [82] | RCT multicenter | 6425 | Hospitalized patients with suspected or laboratory confirmed COVID-19 | DXM 6 mg (IV or orally) during 10 days vs. usual care | PEP 28 d mortality Overall: DXM 482/2104 (22.9%); Pl 1110/4321 (25.7%) (age-adjusted RR 0.83; 95% CI [0.75 to 0.93]; p < 0.001) >sub group mechanical ventilation (1007): 29.3% vs. 41.4%; RR 0.64; 95% CI [0.51 to 0.81] |
Tomazini et al., CoDEX, [84] | RCT multicenter | 299/350 | COVID-19 infection suspected or confirmed, receiving IMV within 48H of meeting criteria for moderate to severe ARDS 2012 | DXM 20 mg daily for 5 days followed by 10 mg daily for 5 days | PEP Ventilator-free days (alive + free from IMV) DXM 6.6 95% CI [5.0 to 8.2) vs. Pl 4.0 95% CI [2.9 to 5.4] difference 4.0 95% CI [2.9 to 5.4] |
Dequin et al., CAPE COVID [92] | RCT multicenter | 149/290 | Confirmed or suspected SARS-CoV-2 + 1 severity criteria IMV (PEEP > 5 cm H2O), p/F < 300 HFOT > 50% Fi, PaO2/FiO2 < 300 FMOT (specified charts), PSI > 130 | HSHC 200 mg daily for 4 to 7 then 100 mg daily for 2 to 4 days then 50 mg daily for 2 to 3 days total 8 days | PEP: 21-day treatment failure (death or persistent dependency on mechanical ventilation or high-flow oxygen therapy HSHC 42.1% vs. pl 50.7% Difference −8.6% [95.48% CI, −24.9% to 7.7%]; p = 0.29) |
Angus et al., REMAP CAP- [85] | RCT multicenter | 384 | COVID-19 suspected or confirmed, severe ICU for Respiratory failure (invasive or non-invasive IMV or HFN flow rate > 30 L/m, and FI > 40% Cardiovascular failure: vaopressor/inotrope | 3 randomization arms Fixed: HSHC 50 mg every 6 h daily for 7 days Shock: HSHC 50 mg/6 h for 7 days while in shock No HSHC Or 200 mg/6 h for 7 days | PEP Composite of hospital mortality and ICU organ support-free days to day 21 Fixed 0 QR, −1 to 15; OR 1.43 95% CI [0.91 to 2.27] Shock 0 IQR, –1 to 13; OR1.22 95% CI [0.76–1.94] None 0 0 (IQR, −1 to 11) |
Barros et al., MetCOVID [86] | RCT single center | 246 | Clinical-radiological suspicion of COVID-19 Sat ≤ 94% in room air or Requiring O2 or IMV | MPS IV 0.5 mg/kg every 12 h × 5 days | PEP pulmonary function testing at day 120 follow-up visit. (Pulmonary function and maximal respiratory pressure testing, DASI, 6MWT) FEV1 (2.6, [0.7], p = 0.01) and FVC (3.2, [0.8], p = 0.01 |
Dequin et al., CAPE COD, [54] | RCT multicenter | 795 | Severe community-acquired pneumoniae, defined by the presence of at least one of four following criteria The initiation of MV (invasive or noninvasive) with a positive end-expiratory pressure level ≥ 5 cm of water The initiation of the administration of oxygen through a HFOT with a ratio of PaO2:FiO2 < 300, with a FiO2 of 50% or more; For patients wearing a non-rebreathing mask, an estimated PaO2:FiO2 ratio < 300, or a score of more than 130 on the Pulmonary Severity Index, which classifies patients with community-acquired pneumonia into five groups according to increasing severity, with a score of more than 130 defining group V | HSHC continuous IV 200 mg/day during the first 4 days. On day 4, regarding medical decision based on predefined criteria, following administration for a total of 8 or 14 days | PEP mortality at day 28 HSHC 25 of 400 patients 6.2%; 95% CI, [3.9 to 8.6] vs. placebo 47 of 395 patients 11.9%; 95% CI, [8.7 to 15.1] (Absolute difference, −5.6 percentage points; 95% CI, [−9.6 to −1.7]; p = 0.006). |
Dose | Author, Reference | Type | Sample Size | Study Population | Treatment | Results |
---|---|---|---|---|---|---|
High Dose | Bone et al. [68] | RCT multicenter | 382 (304 randomized) | Sepsis define as fever or hypothermia rectal T° >38.3 or <35.5 °C tachypnea (>20 bpm), tachycardia (>90 bpm) one of the following indices of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels or oliguria | MPS, 30 mg/kg, every six hours for 48 h vs. placebo | PEP: ARDS development MPS 50/152 32% Pl: 38/152 25% (p = 0.1) SEP: Reverse ARDS MPS 15/50 (31%); Pl: 23/38 (61%) (p = 0.005) 14 d mortality MPS 26/50 (52%); Pl 8/22 (%) (p = 0.004) |
Bernard et al. [63] | RCT multicenter | 99 | ARDS Partial pressure of oxygen ≤70 mm Hg on >40% oxygen, PaO2/PAO2 ratio <0.3, bilateral lung infiltrates, pulmonary artery wedge pressure ≤18 mm Hg | MPS 30 mg/kg IV 6 hourly for 24 h vs. placebo | PEP mortality MPS 30/50 (60%); Pl 31/49 (63.2) OR 0.75 [0.4 to 1.57] p = 0.74 SEP reversal of ARDS MPS 18/50 (39%); Pl 19/49 (36%) (p = 0.07) | |
High- Moderate Dose | Tomazini et al., CoDEX, [84] | RCT multicenter | 299/350 | COVID-19 moderate to severe ARDS according to Berlin, mechanical ventilation | DXM 20 mg daily for 5 days followed by 10 mg daily for 5 days | PEP Ventilator-free days (alive + free from IMV) DXM 6.6 95% CI% [5.0 to 8.2] vs. Pl 4.0 95% CI [2.9 to 5.4] difference 4.0 95% CI [2.9 to 5.4] SEP 28 d mortality all cause no difference |
Barros et al., MetCOVID, [86] | RCT single center | 246 | In hospital COVID-19 Requiring O2 or IMV | MPS IV 0.5 mg/kg every 12 h × 5 days | PEP pulmonary function testing at day 120 follow-up visit. (pulmonary function and maximal respiratory pressure testing, DASI, 6MWT) FEV1 (2.6, [0.7], p = 0.01) and FVC (3.2, [0.8], p = 0.01 | |
Munch et al., COVIDSTEROID, [87] | RCT multicenter | 982/1000 | Confirmed COVID-19 with > 10 L/mn O2 or IMV | DXM 12 mg/d vs. DXM 6 mg/d for 10 days | PEP number of days alive without life support at 28 d 22 d vs. 20.5 d adjusted mean difference, 1.3 days 95% CI [0 to 2.6 days]; p = 0.07 | |
Bouadma et al., COVIDICUS, [88] | RCT multicenter | 546 | Admitted to ICU within 48H for confirmed or highly suspected COVID-19 AHRF (PaO2 < 70 mm Hg, SpO2 < 90%, tachypnea > 30 mn, labored breathing, respiratory distress, or need of O2 flow ≥ 6 L/mn) | DXM 6 mg/d for 10 days (or placebo prior to RECOVERY result communication) or Dexamethasone 20 mg/d for 5 days followed by Dexamethasone 10 mg/d for 5 days | PEP day 60 all-cause mortality Low 26.8% vs. High 25.9% Absolute risk difference −0.8% 95% CI [−8.3 to 6.5] HR, 0.96 95% CI [0.69 to 1.33]; (p = 0.79) | |
Low Dose | Dequin et al., CAPE COVID, [92] | RCT multicenter | 149/290 | Confirmed or suspected SARS-CoV-2 + 1 severity criteria IMV (PEEP > 5 cm H2O), p/F < 300 HFOT > 50% Fi, PaO2/FiO2 < 300 FMOT (specified charts), PSI > 130 Excluded septic shock Low recruitment | HSHC 200 mg daily for 4 to 7 then 100 mg daily for 2 to 4 days then 50 mg daily for 2 to 3 days total 8 days | PEP: 21-day treatment failure (death or persistent dependency on mechanical ventilation or high-flow oxygen therapy HSHC 42.1% vs. pl 50.7% Difference −8.6% 95.48% CI [−24.9% to 7.7%]; p = 0.29) SEP 21 d mortality HSHC 14.7% vs. placebo 27.4% difference −12.7% 95% CI [−25.7% to 0.3%]; p = 0.06 |
Angus et al., REMAP CAP, [85] | RCT multicenter | 384 | COVID-19 suspected or confirmed, severe ICU for Respiratory failure (invasive) or noninvasive MV or HFN flow rate > 30 L/m, and FI > 40% Cardiovascular failure: vasopressor/inotrope Stop ethical | 3 randomization arms Fixed: HSHC 50 mg every 6 h daily for 7 days Shock: HSHC 50 mg/6 h for 7 days while in shock No HSHC Or 200 mg/6 h for 7 days | PEP Composite of hospital mortality and ICU organ support-free days to day 21 Fixed 0 QR, −1 to 15; OR 1.43 95% CI [0.91 to 2.27] Shock 0 IQR, −1 to 13; OR1.22 95% CI [0.76 to 1.94] None 0 0 (IQR, −1 to 11) SEP 28 d mortality Fixed 30%; OR 1.03 95% CI [0.53 to 1.95] Shock 26%;1.10 95% CI [0.58 to 2.11] None 33% | |
Horby et al., RECOVERY, [82] | RCT multicenter | 6425 | hospitalized patients with suspected or laboratory confirmed COVID-19 | DXM 6 mg (IV or orally) for 10 days vs. usual care | PEP 28 d mortality Overall: DXM 482/2104 (22.9%); Pl 1110/4321 (25.7%) (age-adjusted RR 0.83; 95% CI [0.75 to 0.93]; p < 0.001) >sub group mechanical ventilation (1007): 29.3% vs. 41.4%; RR 0.64; 95% CI [0.51 to 0.81) SEP Invasive mechanical ventilation or death RR 0.93; 95% CI [0.85 to 1.01] | |
Corral- Gudino et al., GLUCOCOVID, [93] | RCT multicenter | 64/180 Low recruitment | Symptom > 7 days Radiological evidence of lung disease on chest X-ray or CT-scan Moderate to severe disease with abnormal gas exchange: (PaO2/FiO2 or PaFi) < 300 Or (SaO2/FiO2 or SaFi) < 400 Or ≥2 criteria of the BRESCIA-COVID Respiratory Severity Scale (BCRSS Evidence of a systemic inflammatory response: serum C-reactive protein > 15 mg/dL, D-dimer > 800 ng/mL, ferritin > 1000 mg/dL, or IL-6 levels > 20 pg/mL | MPS 40 mg IV q12 × 3 days and then 20 mg q12 h × 3 days | PEP: Composite endpoint (in-hospital all-cause mortality, escalation to ICU admission, or progression of respiratory insufficiency that required noninvasive ventilation) In ITT: MPS 40% vs. Pl 48% p = 0.25 In PP: RR 0.42 95% CI [0.20 to 0.89] |
3. Summary
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Kuperminc, E.; Heming, N.; Carlos, M.; Annane, D. Corticosteroids in ARDS. J. Clin. Med. 2023, 12, 3340. https://doi.org/10.3390/jcm12093340
Kuperminc E, Heming N, Carlos M, Annane D. Corticosteroids in ARDS. Journal of Clinical Medicine. 2023; 12(9):3340. https://doi.org/10.3390/jcm12093340
Chicago/Turabian StyleKuperminc, Emmanuelle, Nicholas Heming, Miguel Carlos, and Djillali Annane. 2023. "Corticosteroids in ARDS" Journal of Clinical Medicine 12, no. 9: 3340. https://doi.org/10.3390/jcm12093340