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PACULit Literature Updates September 2025: Emergency Medicine & Critical Care

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  1. Use of a drug-related problem oriented medical record in the medication review of critically ill patients Randomized clinical trial
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  2. PACULit Daily Literature Update: Stress hyperglycemia ratio as a biomarker for early mortality risk stratification in cardiovascular disease a propensity matched analysis
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    1 Quiz
  3. PACULit Daily Literature Update: Initial serum electrolyte imbalances and mortality in patients with traumatic brain injury a retrospective study
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    1 Quiz
  4. PACULit Daily Literature Update: AsNeeded AlbuterolBudesonide in Mild Asthma
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  5. PACULit Daily Literature Update: Thiamine as a metabolic resuscitator after in hospital cardiac arrest
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  6. PACULit Daily Literature Update: The Effect of Early Fluid Resuscitation on Mortality in Sepsis A Systematic Review and Meta Analysis
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  7. PACULit Daily Literature Update: Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial
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  8. PACULit Daily Literature Update: Prevalence risk factors and consequences of early clinical deterioration under noninvasive ventilation in emergency department patients a prospective multicentre observational study of the French IRU Network
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  9. PACULit Daily Literature Update: Evaluation of Stress Dose Hydrocortisone Tapers in Septic Shock
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  10. Opportunistic Screening for Atrial Fibrillation With Continuous ECG Monitoring in the Emergency Department
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  11. PACULit Daily Literature Update: Efficacy of targeting high mean arterial pressure for older patients with septic shock OPTPRESS a multicentre pragmatic open label randomised controlled trial
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  12. PACULit Daily Literature Update: Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients
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  13. PACULit Daily Literature Update: Andexanet alfa increases 30-day thrombotic events relative to four-factor prothrombin complex concentrate for factor Xa inhibitors related intracerebral hemorrhage in veterans
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  14. PACULit Daily Literature Update: Antibiotic De-Escalation Practices in the Intensive Care Unit A Multicenter Observational Study
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  15. PACULit Daily Literature Update: Fludrocortisone to treat patients with aneurysmal subarachnoid haemorrhage Protocol for an international phase 3 randomised placebocontrolled multicentre trial
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  16. PACULit Daily Literature Update: Early intramuscular adrenaline administration is associated with improved survival from out-of-hospital cardiac arrest
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  17. PACULit Daily Literature Update: Real-Time Hemodynamic Responses to Epinephrine and Their Association with ROSC in Out-of-Hospital Cardiac Arrest
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  18. Reevaluating bicarbonate therapy in pediatric DKA A propensity scorematched analysis of neurological and respiratory outcomes
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  19. PACULit Daily Literature Update: Establishing discordance rate of estimated glomerular filtration rate between serum creatinine based calculations and cystatin C based calculations in critically ill patients
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  20. Alteplase for Posterior Circulation Ischemic Stroke at 45 to 24 Hours
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  21. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
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    2 Quizzes
  22. ACPE Required Forms: PACULit Literature Updates September 2025: Emergency Medicine & Critical Care
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Daily Literature Update

Fludrocortisone to treat patients with aneurysmal subarachnoid haemorrhage Protocol for an international phase 3 randomised placebocontrolled multicentre trial

Cohen J, Delaney A, Udy A, et al. Fludrocortisone to treat patients with aneurysmal subarachnoid haemorrhage: Protocol for an international, phase 3, randomised, placebo-controlled, multicentre trial. Crit Care Resusc. 2025 Jun;27(2):100116-. doi: 100116. PMID: 40677678.

Study Type: International phase 3 randomised, placebo-controlled, multicentre trial protocol

Population: Patients with aneurysmal subarachnoid haemorrhage (aSAH)

Intervention: Fludrocortisone (synthetic mineralocorticoid) vs placebo to treat hyponatraemia

Outcomes: Effect on hyponatraemia incidence and clinical outcomes including delayed cerebral ischemia and death/disability

Key Findings

  • Hyponatraemia common after aSAH and linked to worse outcomes.
  • Fludrocortisone may reduce natriuresis and volume depletion by mitigating cerebral salt wasting syndrome.
  • Previous smaller studies showed reduced negative sodium balance and possible lower risk of death/disability with use.
  • However, overall current evidence lacks definitive proof for improved clinical outcomes.
  • This large phase 3 trial aims to clarify fludrocortisone’s role in treatment of aSAH-associated hyponatraemia and outcomes.

Context & Related Research

  • Maeda et al., 1989: RCT showed fludrocortisone reduced negative sodium balance post-aSAH (PMID:2672426)
  • Huang et al., 2023: Retrospective analysis found fludrocortisone linked to lower 90-day death/disability risk (PMID:37808869)
  • Qureshi et al., 2017: Systematic review found no significant benefits of mineralocorticoids on clinical outcomes (PMID:28987848)
  • Kaneko et al., 2016: Meta-analysis reported corticosteroids reduced natriuresis but not neurological outcomes or symptomatic vasospasm (reference.medscape.com, PMID:27173669)
  • Current gaps: Need for rigorous large trials to confirm if fludrocortisone improves morbidity and mortality post-aSAH

Strengths & Limitations

Strengths Limitations
Multicentre, international, phase 3 RCT design Protocol stage; no outcome data yet
Largest trial planned to evaluate mineralocorticoid therapy in aSAH Potential variability in standard of care across centres
Focus on both biochemical and clinically important endpoints Hyponatraemia mechanistic complexity may limit generalisability

Clinical Implications & Impact

Pharmacists should monitor sodium and volume status closely in aSAH patients. Fludrocortisone, if proven effective, could be incorporated into protocols to prevent or correct hyponatraemia and reduce complications. Awareness of mineralocorticoid side effects and dosing schedules will be critical. Early intervention targeting cerebral salt wasting may improve patient outcomes and decrease ICU length of stay.

Conclusion

Current evidence highlights fludrocortisone’s potential to mitigate hyponatraemia after aneurysmal subarachnoid haemorrhage; definitive clinical outcome data await results of this phase 3 trial.

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Citations

  • Cohen J et al. Crit Care Resusc. 2025 Jun;27(2):100116-. PMID:40677678
  • Maeda M et al. Stroke. 1989;20(2):267–274. PMID:2672426
  • Huang Y et al. Neurocrit Care. 2023;38(3):450–460. PMID:37808869
  • Qureshi AI et al. J Neurosurg. 2017;126(4):1134–1142. PMID:28987848
  • Kaneko J et al. Stroke. 2016;47(6):1440–1445. PMID:27173669

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