Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.
Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, Gibson M, Umberger R.
OBJECTIVE: To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: ICUs of five hospitals in Memphis.
PARTICIPANTS: Ninety-one patients with severe early ARDS (= 72 h), 66% with sepsis.
INTERVENTIONS: Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.
MAIN OUTCOME MEASURE: The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.
RESULTS: In intention-to-treat analysis, the response of the two groups (63 treated and 28 control) clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever.
CONCLUSIONS: Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay.
Em Chest. 2007 Apr;131(4):954-63.
Neste estudo o grupo do Dr Meduri demonstrou haver redução mais pronunciada da resposta inflamatória (medida por Proteina C Reativa no plasma), bem como melhoras acentuadas na PaO2/FiO2 no grupo que usou metilprednisolona quando comparado a placebo. Houve ainda redução de disfunções orgânicas e tempo de ventilação e tempo em UTI. Os resultados impressionantes não se refletiram em redução de mortalidade uma vez que o estudo não tinha poder suficiente para este desfecho.