Hydrocortisone in Severe Community-Acquired Pneumonia

Dequin, Pierre‐François; Meziani, Ferhat; Quenot, Jean-Pierre; Kamel, Toufik; Ricard, Jean‐Damien; Badié, Julio; Reignier, Jean; Heming, Nicholas; Plantefève, Gaëtan; Souweine, Bertrand; Voiriot, Guillaume; Colin, Gwenhaël; Frat, Jean‐Pierre; Mira, Jean‐Paul; Barbarot, Nicolas; François, Bruno; Louis, Guillaume; Gibot, Sébastien; Guitton, Christophe; Giacardi, Christophe; Hraiech, Sami; Vimeux, Sylvie; L’Her, Erwan; Faure, Henri; Herbrecht, Jean-Étienne; Bouisse, Camille; Joret, Aurélie; Terzi, Nicolas; Gacouin, Arnaud; Quentin, Charlotte; Jourdain, M.; Leclerc, Marie; Coffre, Carine; Bourgoin, Hélène; Lengelle, Céline; Caille-Fénérol, Caroline; Giraudeau, Bruno; Gouge, Amélie Le

doi:10.1056/nejmoa2215145

Cited by 160 publications

(159 citation statements)

References 29 publications

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“…This apparent discord between the results of ESCAPe [39] and Dequin et al [38 ▪▪ ] is important to analyze (Table 1). There were several key differences between the studies.…”

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 92%

“…The subjects in ESCAPe [39], from a US Veterans Affairs hospital system, were almost exclusively male. On the other hand, one third of subjects in Dequin et al [38 ▪▪ ] were female, and analysis showed a markedly favorable response in women and marginal response in men. Gender differences in critical care are well known, including the higher mortality rate in men from sCAP.…”

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 94%

“…Therefore, the role of corticosteroids as immune modulators favoring the downregulation of this systemic response has been widely discussed, yet with conflicting results [2]. A phase 3 multicenter trial by Dequin et al [38 ▪▪ ], found a trend towards lower mortality by day 28 in patients receiving hydrocortisone therapy compared to placebo. Regarding safety outcomes, corticosteroids were associated with increased incidence of hyperglycemia, but not with infections or gastrointestinal bleeding.…”

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 99%

“…There were several key differences between the studies. ESCAPe [39] used methylprednisolone and allowed steroids to be given for up to 96 h after meeting admission criteria; whilst Dequin et al [38 ▪▪ ] assessed the use of hydrocortisone starting within the first 24 h. Both, the type of corticosteroid and the therapeutic window may be critical. Another key difference between the studies is gender.…”

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 99%

“…Understanding if there are gender-specific effects of interventions is critical to developing effective personalized care. Moreover, it is notable that Dequin et al [38 ▪▪ ] excluded patients with influenza.…”

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 99%

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Severe community-acquired pneumonia in the post COVID-19 era

Ruiz-Spinelli,

Waterer,

Rello

2023

Current Opinion in Critical Care

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Purpose of review The aim was to examine and summarize the most recent published literature in the last years stating the advances for treatment options and adjunctive therapies in patients hospitalized with severe community-acquired pneumonia (sCAP). Search was performed in PubMed, including observational studies, randomized controlled trials, systematic reviews and meta-analyses, and international guidelines. Recent findings Regardless of a large number of published CAP guidelines, most of their recommendations are based on low-level evidence. Viruses have an increasing role as sCAP etiology with an impact on mortality. Accordingly, it is imperative to strengthen the demand for vaccines and newer antivirals. Considering an early monitoring of the immune response in patients with severe Influenza, may help to evaluate a personalized immunomodulatory strategy. Despite growing evidence, the use of corticosteroids as an adjunctive therapy in bacterial sCAP continues to be controversial. Summary Mortality due to sCAP still remains undesirably high. This fact strengthens the need for more high-quality research to increase evidence. It also highlights the need for clinicians to be aware of the level of evidence of the stated recommendations, taking this into consideration before decision making.

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“…This apparent discord between the results of ESCAPe [39] and Dequin et al [38 ▪▪ ] is important to analyze (Table 1). There were several key differences between the studies.…”

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 92%

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 94%

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 99%

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 99%

Section: Adjunctive Therapies For Severe Community-acquired Pneumonia...mentioning

confidence: 99%

See 3 more Smart Citations

Severe community-acquired pneumonia in the post COVID-19 era

Ruiz-Spinelli,

Waterer,

Rello

2023

Current Opinion in Critical Care

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Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Shan,

Pu,

et al. 2024

JAMA

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ImportanceIt is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy.ObjectiveTo assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO.Design, Setting, and ParticipantsThis investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy.Main Outcomes and MeasuresThe primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours.ResultsAmong 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo.Conclusions and RelevanceAmong patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR2100051729

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Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections

Pirracchio,

Venkatesh,

Legrand

2024

JAMA

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ImportanceSevere pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults worldwide. Pulmonary infections in critically ill patients may cause septic shock, acute respiratory distress syndrome, or both, which are associated with mortality rates ranging between 30% and 50%.ObservationsCorticosteroids mitigate the immune response to infection and improve outcomes for patients with several types of severe pulmonary infections. Low-dose corticosteroids, defined as less than or equal to 400 mg hydrocortisone equivalent daily, can reduce mortality of patients with severe COVID-19, community-acquired pneumonia, and Pneumocystis pneumonia. A randomized clinical trial of 6425 patients hospitalized with COVID-19 who required supplemental oxygen or noninvasive or invasive mechanical ventilation reported that dexamethasone 6 mg daily for 10 days decreased 28-day mortality (23% vs 26%). A meta-analysis that included 7 randomized clinical trials of 1689 patients treated in the intensive care unit for severe bacterial community-acquired pneumonia reported that hydrocortisone equivalent less than or equal to 400 mg daily for 8 days or fewer was associated with lower 30-day mortality compared with placebo (10% vs 16%). In a meta-analysis of 6 randomized clinical trials, low-dose corticosteroids were associated with lower mortality rates compared with placebo for patients with HIV and moderate to severe Pneumocystis pneumonia (13% vs 25%). In a predefined subgroup analysis of a trial of low-dose steroid treatment for septic shock, patients with community-acquired pneumonia randomized to 7 days of intravenous hydrocortisone 50 mg every 6 hours and fludrocortisone 50 μg daily had decreased mortality compared with the placebo group (39% vs 51%). For patients with acute respiratory distress syndrome caused by various conditions, low-dose corticosteroids were associated with decreased in-hospital mortality (34% vs 45%) according to a meta-analysis of 8 studies that included 1091 patients. Adverse effects of low-dose corticosteroids may include hyperglycemia, gastrointestinal bleeding, neuropsychiatric disorders, muscle weakness, hypernatremia, and secondary infections.Conclusions and RelevanceTreatment with low-dose corticosteroids is associated with decreased mortality for patients with severe COVID-19 infection, severe community-acquired bacterial pneumonia, and moderate to severe Pneumocystis pneumonia (for patients with HIV). Low-dose corticosteroids may also benefit critically ill patients with respiratory infections who have septic shock, acute respiratory distress syndrome, or both.

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Hydrocortisone in Severe Community-Acquired Pneumonia

Cited by 160 publications

References 29 publications

Severe community-acquired pneumonia in the post COVID-19 era

Severe community-acquired pneumonia in the post COVID-19 era

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections

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