2006 Efficacy and safety of corticosteroids for persistent acute respiratory distress

N Engl J Med. 2006 Apr 20;354(16):1671-84.

Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT,
Ancukiewicz M; National Heart, Lung, and Blood Institute Acute Respiratory
Distress Syndrome (ARDS) Clinical Trials Network.

Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box
359762, 325 Ninth Ave., Seattle, WA 98104, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is
characterized by excessive fibroproliferation, ongoing inflammation, prolonged
mechanical ventilation, and a substantial risk of death. Because previous reports
suggested that corticosteroids may improve survival, we performed a multicenter,
randomized controlled trial of corticosteroids in patients with persistent ARDS.
METHODS: We randomly assigned 180 patients with ARDS of at least seven days'
duration to receive either methylprednisolone or placebo in a double-blind
fashion. The primary end point was mortality at 60 days. Secondary end points
included the number of ventilator-free days and organ-failure-free days,
biochemical markers of inflammation and fibroproliferation, and infectious
complications. RESULTS: At 60 days, the hospital mortality rate was 28.6 percent
in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and
29.2 percent in the methylprednisolone group (95 percent confidence interval,
20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95
percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent
confidence interval, 22.8 to 41.7 percent; P=1.0), respectively.
Methylprednisolone was associated with significantly increased 60- and 180-day
mortality rates among patients enrolled at least 14 days after the onset of ARDS.
Methylprednisolone increased the number of ventilator-free and shock-free days
during the first 28 days in association with an improvement in oxygenation,
respiratory-system compliance, and blood pressure with fewer days of vasopressor
therapy. As compared with placebo, methylprednisolone did not increase the rate
of infectious complications but was associated with a higher rate of
neuromuscular weakness. CONCLUSIONS: These results do not support the routine use
of methylprednisolone for persistent ARDS despite the improvement in
cardiopulmonary physiology. In addition, starting methylprednisolone therapy more
than two weeks after the onset of ARDS may increase the risk of death.
(ClinicalTrials.gov number, NCT00295269.). Copyright 2006 Massachusetts Medical

2008 Mechanical ventilation guided by esophageal pressure in acute lung injury.

N Engl J Med. 2008 Nov 13;359(20):2095-104. Epub 2008 Nov 11.

Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring

Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess
Medical Center, Boston 02215, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

BACKGROUND: Survival of patients with acute lung injury or the acute respiratory
distress syndrome (ARDS) has been improved by ventilation with small tidal
volumes and the use of positive end-expiratory pressure (PEEP); however, the
optimal level of PEEP has been difficult to determine. In this pilot study, we
estimated transpulmonary pressure with the use of esophageal balloon catheters.
We reasoned that the use of pleural-pressure measurements, despite the technical
limitations to the accuracy of such measurements, would enable us to find a PEEP
value that could maintain oxygenation while preventing lung injury due to
repeated alveolar collapse or overdistention. METHODS: We randomly assigned
patients with acute lung injury or ARDS to undergo mechanical ventilation with
PEEP adjusted according to measurements of esophageal pressure (the
esophageal-pressure-guided group) or according to the Acute Respiratory Distress
Syndrome Network standard-of-care recommendations (the control group). The
primary end point was improvement in oxygenation. The secondary end points
included respiratory-system compliance and patient outcomes. RESULTS: The study
reached its stopping criterion and was terminated after 61 patients had been
enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of
inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided
group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002).
This effect was persistent over the entire follow-up time (at 24, 48, and 72
hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system
compliance was also significantly better at 24, 48, and 72 hours in the
esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of
variance). CONCLUSIONS: As compared with the current standard of care, a
ventilator strategy using esophageal pressures to estimate the transpulmonary
pressure significantly improves oxygenation and compliance. Multicenter clinical
trials are needed to determine whether this approach should be widely adopted.
(ClinicalTrials.gov number, NCT00127491.) 2008 Massachusetts Medical Society