2006 Comparison of two fluid-management strategies in acute lung injury
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome
(ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson
BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL.
Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic,
9500 Euclid Ave., Desk A-90, Cleveland, OH 44195, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.
BACKGROUND: Optimal fluid management in patients with acute lung injury is
unknown. Diuresis or fluid restriction may improve lung function but could
jeopardize extrapulmonary-organ perfusion. METHODS: In a randomized study, we
compared a conservative and a liberal strategy of fluid management using explicit
protocols applied for seven days in 1000 patients with acute lung injury. The
primary end point was death at 60 days. Secondary end points included the number
of ventilator-free days and organ-failure-free days and measures of lung
physiology. RESULTS: The rate of death at 60 days was 25.5 percent in the
conservative-strategy group and 28.4 percent in the liberal-strategy group
(P=0.30; 95 percent confidence interval for the difference, -2.6 to 8.4 percent).
The mean (+/-SE) cumulative fluid balance during the first seven days was
-136+/-491 ml in the conservative-strategy group and 6992+/-502 ml in the
liberal-strategy group (P<0.001). As compared with the liberal strategy, the
conservative strategy improved the oxygenation index ([mean airway pressure x the
ratio of the fraction of inspired oxygen to the partial pressure of arterial
oxygen]x100) and the lung injury score and increased the number of
ventilator-free days (14.6+/-0.5 vs. 12.1+/-0.5, P<0.001) and days not spent in
the intensive care unit (13.4+/-0.4 vs. 11.2+/-0.4, P<0.001) during the first 28
days but did not increase the incidence or prevalence of shock during the study
or the use of dialysis during the first 60 days (10 percent vs. 14 percent,
P=0.06). CONCLUSIONS: Although there was no significant difference in the primary
outcome of 60-day mortality, the conservative strategy of fluid management
improved lung function and shortened the duration of mechanical ventilation and
intensive care without increasing nonpulmonary-organ failures. These results
support the use of a conservative strategy of fluid management in patients with
acute lung injury. (ClinicalTrials.gov number, NCT00281268
[ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
2006 Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome
(ARDS) Clinical Trials Network, Wheeler AP, Bernard GR, Thompson BT, Schoenfeld
D, Wiedemann HP, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL.
Vanderbilt University, Nashville, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.
BACKGROUND: The balance between the benefits and the risks of pulmonary-artery
catheters (PACs) has not been established. METHODS: We evaluated the relationship
of benefits and risks of PACs in 1000 patients with established acute lung injury
in a randomized trial comparing hemodynamic management guided by a PAC with
hemodynamic management guided by a central venous catheter (CVC) using an
explicit management protocol. Mortality during the first 60 days before discharge
home was the primary outcome. RESULTS: The groups had similar baseline
characteristics. The rates of death during the first 60 days before discharge
home were similar in the PAC and CVC groups (27.4 percent and 26.3 percent,
respectively; P=0.69; absolute difference, 1.1 percent; 95 percent confidence
interval, -4.4 to 6.6 percent), as were the mean (+/-SE) numbers of both
ventilator-free days (13.2+/-0.5 and 13.5+/-0.5; P=0.58) and days not spent in
the intensive care unit (12.0+/-0.4 and 12.5+/-0.5; P=0.40) to day 28. PAC-guided
therapy did not improve these measures for patients in shock at the time of
enrollment. There were no significant differences between groups in lung or
kidney function, rates of hypotension, ventilator settings, or use of dialysis or
vasopressors. Approximately 90 percent of protocol instructions were followed in
both groups, with a 1 percent rate of crossover from CVC- to PAC-guided therapy.
Fluid balance was similar in the two groups, as was the proportion of
instructions given for fluid and diuretics. Dobutamine use was uncommon. The PAC
group had approximately twice as many catheter-related complications
(predominantly arrhythmias). CONCLUSIONS: PAC-guided therapy did not improve
survival or organ function but was associated with more complications than
CVC-guided therapy. These results, when considered with those of previous
studies, suggest that the PAC should not be routinely used for the management of
acute lung injury. (ClinicalTrials.gov number, NCT00281268.). Copyright 2006
Massachusetts Medical Society.
2006 Efficacy and safety of corticosteroids for persistent acute respiratory distress
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
Society.
2008 Mechanical ventilation guided by esophageal pressure in acute lung injury.
Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring
SH.
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