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Huang, S. Hydrocortisone in Community Acquired Pneumonia. Encyclopedia. Available online: https://encyclopedia.pub/entry/57345 (accessed on 16 November 2024).
Huang S. Hydrocortisone in Community Acquired Pneumonia. Encyclopedia. Available at: https://encyclopedia.pub/entry/57345. Accessed November 16, 2024.
Huang, Samuel. "Hydrocortisone in Community Acquired Pneumonia" Encyclopedia, https://encyclopedia.pub/entry/57345 (accessed November 16, 2024).
Huang, S. (2024, November 03). Hydrocortisone in Community Acquired Pneumonia. In Encyclopedia. https://encyclopedia.pub/entry/57345
Huang, Samuel. "Hydrocortisone in Community Acquired Pneumonia." Encyclopedia. Web. 03 November, 2024.
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Summary of Key Findings Oxygenation and Respiratory Outcomes: Hydrocortisone significantly improved oxygenation (PaO₂/FiO₂ ratio) and increased the number of mechanical ventilation-free days. This suggests that hydrocortisone could be beneficial in enhancing respiratory outcomes. Reduction in Major Complications: There was a notable reduction in the incidence of major complications, including delayed septic shock and MODS, among patients treated with hydrocortisone. Mortality: ICU, hospital, and 60-day mortality were significantly lower in the hydrocortisone group, indicating a potential survival benefit. Length of Stay and Ventilation Duration: Patients in the hydrocortisone group had shorter ICU stays, hospital stays, and duration on mechanical ventilation, supporting its efficacy in reducing the burden of intensive care needs. Safety Profile: Although complications like ARDS, ventilator-associated pneumonia, and acute renal failure were monitored, there were no significant increases in these adverse events with hydrocortisone. This supports its safety profile in the ICU setting.
pneumonia
Cape Cod
Hydrocortisone
1. Introduction
| Variable | Confalonieri 2012 | Nafae 2013 | Cape Cod 2023 |
| Mortality Outcomes | |||
| ICU Mortality | 7/23 (30%) Placebo, 0/23 (0%) Hydrocortisone | Not reported | Not reported |
| 28-day Mortality | Not reported | Not reported | 47/395 (11.9%) Placebo, 25/400 (6.2%) Hydrocortisone |
| 60-day Mortality | 8/23 (35%) Placebo, 0/23 (0%) Hydrocortisone | Not reported | Not reported |
| Hospital Mortality | 7/23 (30%) Placebo, 0/23 (0%) Hydrocortisone | 6/20 (30%) Placebo, 4/60 (6.7%) Hydrocortisone | Not reported |
| Mechanical Ventilation | |||
| Need for Mechanical Ventilation | 15/23 (65%) Placebo, 6/23 (26%) Hydrocortisone | 5/20 (25%) Placebo, 8/60 (13.3%) Hydrocortisone | 65/220 (29.5%) Placebo, 40/222 (18%) Hydrocortisone |
| Mechanical Ventilation-Free Days | 0 (0-6) Placebo, 4 (0-7) Hydrocortisone | Not reported | Not reported |
| Duration of Mechanical Ventilation | 10 (2-44) days Placebo, 4 (1-27) days Hydrocortisone | 12-22 days Placebo, 5-24 days Hydrocortisone | Not reported |
| PaO₂/FiO₂ Ratio | |||
| Baseline PaO₂/FiO₂ Ratio | 237 ± 92 Placebo, 332 ± 80 Hydrocortisone | 319.4 ± 54.3 Placebo, 343.9 ± 51.6 Hydrocortisone | Not reported |
| PaO₂/FiO₂ Improvement ≥ 100 | 8/23 (35%) Placebo, 20/23 (87%) Hydrocortisone | Not reported | Not reported |
| Inflammatory Markers | |||
| CRP (mg/L) - Baseline | 34 (0–225) Placebo, 18 (0–44) Hydrocortisone | 95.4 ± 45.64 Placebo, 91.3 ± 39.96 Hydrocortisone | Not reported |
| CRP (mg/L) - Reduction | Not reported | 43.7 ± 46.2 Placebo, 16.3 ± 18.9 Hydrocortisone | Not reported |
| ESR (mm/hr) | Not reported | 81.7 ± 6 Placebo, 79.9 ± 9.7 Hydrocortisone | Not reported |
| Length of Stay | |||
| ICU Stay (days) | 18 (3–45) Placebo, 10 (4–33) Hydrocortisone | 6.3 ± 8.2 Placebo, 3.1 ± 4.9 Hydrocortisone | Not reported |
| Total Hospital Stay (days) | 21 (3–72) Placebo, 13 (10–53) Hydrocortisone | 16.5 ± 2.24 Placebo, 9.27 ± 2.4 Hydrocortisone | Not reported |
| Safety and Complications | |||
| Delayed Septic Shock | 10/23 (52%) Placebo, 0/23 (0%) Hydrocortisone | Not reported | Not reported |
| ARDS | 4/23 (17%) Placebo, 0/23 (0%) Hydrocortisone | 6/20 (30%) Placebo, 4/60 (6.7%) Hydrocortisone | Not reported |
| Nosocomial Infection | 4/23 (18%) Placebo, 0/23 (0%) Hydrocortisone | Not reported | 44/395 (11.1%) Placebo, 39/400 (9.8%) Hydrocortisone |
| Gastrointestinal Bleeding | 1/23 (4%) Placebo, 1/23 (4%) Hydrocortisone | 1/20 (5%) Placebo, 1/60 (1.6%) Hydrocortisone | 13/395 (3.3%) Placebo, 9/400 (2.2%) Hydrocortisone |
| Hypokalemia | Not reported | 5/20 (25%) Placebo, 35/60 (58.3%) Hydrocortisone | Not reported |
| Uncontrolled Diabetes (glucose > 250 mg/dL) | Not reported | 8/20 (40%) Placebo, 19/60 (31.7%) Hydrocortisone | Not reported |
| Blood Chemistry and Hematology | |||
| WBC (·10³/cm) | Not reported | 17 ± 4.5 Placebo, 17.8 ± 4.5 Hydrocortisone | Not reported |
| Hematocrit (%) | Not reported | 28.9 ± 2.7 Placebo, 30 ± 4.2 Hydrocortisone | Not reported |
| BUN (mg/dL) | Not reported | 41.8 ± 19.5 Placebo, 31.6 ± 14.2 Hydrocortisone | Not reported |
| Creatinine (mg/dL) | Not reported | 1.5 ± 0.8 Placebo, 1.14 ± 0.5 Hydrocortisone | Not reported |
| Sodium Level (Na, mEq/L) | Not reported | 130.1 ± 3.71 Placebo, 131.9 ± 6 Hydrocortisone | Not reported |
| Potassium Level (K, mEq/L) | Not reported | 3.63 ± 0.44 Placebo, 3.6 ± 0.46 Hydrocortisone | Not reported |
[1][2][3][4][5] Table1. Common Variables and Results Across [6], Nafae 2013, and Cape Cod 2023.
2. Meta-Analysis Table for Key Parameters and Outcomes
| Parameter/Outcome | Placebo | Hydrocortisone | p-Value | Interpretation |
|---|---|---|---|---|
| Demographics | ||||
| Male/Female | 15/8 | 17/6 | 0.53 | No significant difference in gender distribution |
| Age, years | 66.6 ± 14.7 | 60.4 ± 17.3 | 0.20 | No significant age difference |
| Smoking Habit | See subgroup analysis | See subgroup analysis | NS | Not significantly different |
| Severity Scores | ||||
| APACHE II Score | 18.2 ± 4.0 | 17.2 ± 4.1 | 0.39 | No significant difference in severity |
| MODS Score | 1.2 ± 0.4 | 1.2 ± 0.5 | 0.75 | No significant difference |
| Vital Signs and Laboratory Values | ||||
| Temperature (°C) | 38.2 ± 1.2 | 38.3 ± 0.9 | 0.76 | No significant difference |
| WBC Count (×10⁹/L) | 13.9 ± 5.1 | 13.4 ± 5.5 | 0.73 | No significant difference |
| PaO₂/FiO₂ Ratio | 178 ± 58 | 141 ± 49 | 0.03 | Significant difference; lower in hydrocortisone group |
| PaO₂/FiO₂ ≤ 200 | 13 (57%) | 21 (91%) | 0.02 | Significant; worse oxygenation in hydrocortisone group |
| CRP (mg/dL) | 29 (6–200) | 55 (14–349) | 0.04 | Significant; higher CRP in hydrocortisone group |
| Respiratory Support and Ventilation | ||||
| On Mechanical Ventilation | 19 (83%) | 15 (65%) | 0.18 | Not significant |
| Mechanical Ventilation-Free Days | 0 (0–6) | 4 (0–7) | 0.01 | Significant; more vent-free days in hydrocortisone |
| PaO₂/FiO₂ Ratio (after treatment) | 237 ± 92 | 332 ± 80 | 0.0008 | Significant improvement with hydrocortisone |
| PaO₂/FiO₂ Improvement ≥ 100 | 8 (35%) | 20 (87%) | 0.0007 | Significant improvement in oxygenation |
| Chest Radiograph and MODS | ||||
| Chest Radiograph Score | 2.6 ± 1.3 | 1.1 ± 0.7 | < 0.0001 | Significant improvement with hydrocortisone |
| Improvement in Chest Radiograph Score | 5 (22%) | 21 (91%) | < 0.0001 | Significant improvement with hydrocortisone |
| Patients with MODS | 16 (70%) | 8 (35%) | 0.02 | Significant reduction in MODS with hydrocortisone |
| Shock and Complications | ||||
| Delayed Septic Shock by Day 8 | 9 (43%) | 0 (0%) | 0.001 | Significant reduction in delayed septic shock |
| New ARDS by Day 8 | 3 (13%) | 0 (0%) | 0.23 | Not significant |
| Major Complications | ||||
| Major Complications | 18 (78%) | 6 (26%) | < 0.001 | Significant reduction in complications |
| Delayed Septic Shock | 10 (52%) | 0 (0%) | < 0.001 | Significant reduction with hydrocortisone |
| Shock Not Related to Sepsis | 2 (9%) | 0 (0%) | 0.5 | Not significant |
| ARDS | 4 (17%) | 0 (0%) | 0.11 | Not significant |
| Nosocomial Infection | 4 (18%) | 0 (0%) | 0.11 | Not significant |
| Ventilator-Associated Pneumonia | 3 (13%) | 0 (0%) | 0.23 | Not significant |
| Acute Renal Failure | 3 (13%) | 0 (0%) | 0.23 | Not significant |
| Mortality and Survival | ||||
| ICU Mortality | 7 (30%) | 0 (0%) | 0.009 | Significant reduction in ICU mortality |
| Hospital Mortality | 7 (30%) | 0 (0%) | 0.009 | Significant reduction in hospital mortality |
| 60-day Mortality | 8 (38%) | 0 (0%) | 0.001 | Significant reduction in 60-day mortality |
| Length of Stay and Mechanical Ventilation | ||||
| Length of ICU Stay, days | 18 (3–45) | 10 (4–33) | 0.01 | Significant reduction in ICU stay |
| Length of Hospital Stay, days | 21 (3–72) | 13 (10–53) | 0.03 | Significant reduction in hospital stay |
| Duration of Mechanical Ventilation, days | 10 (2–44) | 4 (1–27) | 0.007 | Significant reduction in duration of ventilation |
3. Pathophysiology and Purpose
Q: Why might steroids be beneficial in treating pneumonia?
A: Steroids may help control an excessive inflammatory response associated with infection, which can contribute to disease severity and complications in pneumonia.
Q: What are the main side effects of steroids in pneumonia treatment?
A: Major side effects include hyperglycemia, GI bleeding, increased risk of infections, and neuropsychiatric symptoms.
4. RCTs of Steroids in Pneumonia
Q: What did early RCTs (2005–2015) suggest about the impact of steroids on pneumonia outcomes?
A: Early RCTs showed mixed results:
- Some trials showed reductions in mortality, time to clinical stability, and length of stay, while others did not affect mortality.
- Steroids were generally associated with faster clinical improvement but increased hyperglycemia.
Q: What were limitations of early RCTs on steroids in pneumonia?
A: Limitations included small sample sizes, varied inclusion/exclusion criteria, differences in steroid types and dosing protocols, and potential inclusion of patients with pneumonia mimics.
5. Meta-Analyses Insights
Q: What did meta-analyses reveal about steroid benefits in pneumonia?
A: Meta-analyses suggested that steroids may reduce mortality in severe CAP (community-acquired pneumonia), reduce mechanical ventilation need, shorten ICU stays, and increase clinical stability time. However, steroids consistently increased hyperglycemia.
Q: Are there different guidelines regarding steroids in pneumonia?
A: Yes, the European guidelines (ESICM/SCCM) recommend steroids for severe CAP, while the American (ATS/IDSA) guidelines recommend against them, reflecting ongoing debate.
6. CAPE COD Trial (2023)
Q: What was the main question of the CAPE COD trial?
A: The CAPE COD trial asked if IV hydrocortisone reduces mortality in patients hospitalized with severe CAP.
Q: What were the results of the CAPE COD trial?
A: The trial found:
- A reduction in 28-day mortality (6.2% in the steroid group vs. 11.9% in placebo).
- Lower 90-day mortality and reduced need for intubation or vasopressors in the steroid group.
- Higher insulin requirements in the steroid group, with no increase in GI bleeds or hospital-acquired infections.
Q: Why did the CAPE COD trial show a larger benefit with steroids?
A: Possible reasons include:
- The steroid group had fewer cases of shock compared to placebo.
- The strict inclusion criteria targeted severely ill patients who are more likely to benefit.
- Some patients may have had concurrent ARDS, a condition where steroids are known to be beneficial.
7. Practical Takeaways and Remaining Questions
Q: In which patients with pneumonia might steroids be most beneficial?
A: Steroids appear to benefit patients with severe pneumonia, especially those with high levels of inflammation (e.g., elevated CRP).
Q: What questions remain about the best way to use steroids in CAP?
A: Unanswered questions include:
- Optimal route of administration (IV vs. PO).
- Ideal duration and timing of steroid initiation.
- Best type of steroid for pneumonia treatment.
Q: What is the clinical recommendation regarding steroids in CAP?
A: Clinicians should carefully select patients with severe CAP for steroid treatment, considering the mixed evidence and the potential for side effects like hyperglycemia.
References
- Tyler Pitre; Daniyal Abdali; Dipayan Chaudhuri; Stephen M. Pastores; Andrea M. Nei; Djillali Annane; Bram Rochwerg; Dena Zeraatkar; Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis. J. Gen. Intern. Med.. 2023, 38, 2593-2606.
- Marco Confalonieri; Rosario Urbino; Alfredo Potena; Marco Piattella; Piercarlo Parigi; Giacomo Puccio; Rossana Della Porta; Carbone Giorgio; Francesco Blasi; Reba Umberger; G. Umberto Meduri; Hydrocortisone Infusion for Severe Community-acquired Pneumonia. Am. J. Respir. Crit. Care Med.. 2005, 171, 242-248.
- Pierre-François Dequin; Ferhat Meziani; Jean-Pierre Quenot; Toufik Kamel; Jean-Damien Ricard; Julio Badie; Jean Reignier; Nicholas Heming; Gaëtan Plantefève; Bertrand Souweine; Guillaume Voiriot; Gwenhaël Colin; Jean-Pierre Frat; Jean-Paul Mira; Nicolas Barbarot; Bruno François; Guillaume Louis; Sébastien Gibot; Christophe Guitton; Christophe Giacardi; Sami Hraiech; Sylvie Vimeux; Erwan L’her; Henri Faure; Jean-Etienne Herbrecht; Camille Bouisse; Aurélie Joret; Nicolas Terzi; Arnaud Gacouin; Charlotte Quentin; Mercé Jourdain; Marie Leclerc; Carine Coffre; Hélène Bourgoin; Céline Lengellé; Caroline Caille-Fénérol; Bruno Giraudeau; Amélie Le Gouge; Hydrocortisone in Severe Community-Acquired Pneumonia. New Engl. J. Med.. 2023, 388, 1931-1941.
- Ramadan M. Nafae; Mostafa I. Ragab; Fawzy M. Amany; Shimaa B. Rashed; Adjuvant role of corticosteroids in the treatment of community-acquired pneumonia. Egypt. J. Chest Dis. Tuberc.. 2013, 62, 439-445.
- Matthias Briel; Simone M C Spoorenberg; Dominic Snijders; Antoni Torres; Silvia Fernandez-Serrano; G Umberto Meduri; Albert Gabarrús; Claudine A Blum; Marco Confalonieri; Benjamin Kasenda; Reed Ac Siemieniuk; Wim Boersma; Willem Jan W Bos; Mirjam Christ-Crain; Corticosteroids in Patients Hospitalized With Community-Acquired Pneumonia: Systematic Review and Individual Patient Data Metaanalysis. Clin. Infect. Dis.. 2017, 66, 346-354.
- M. Confalonieri; M. Kodric; M. Santagiuliana; C. Longo; M. Biolo; R. Cifaldi; C. Torregiani; M. Jevnikar; To use or not to use corticosteroids for pneumonia? A clinician’s perspective. Monaldi Arch. Chest Dis.. 2012, 77, 94-101.
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