Treatment

In 40 patients with ARDS, Spragg and coworkers did a Phase I/Phase II randomized trial of a recombinant surfactant protein C-based surfactant (venticute). Patients received one or two doses of exogenous surfactant on four occasions over 24 hours. Treatment was well tolerated. No benefit was noted. At 48 hours, bronchoalveolar lavage reflected exogenous surfactant components, did not show improvement in lowering of surface tension, and had lower level of interleukin-6 than did the control group. Exogenous surfactant was not detected in lavage fluid at 120 hours. The authors conclude that a recombinant protein C-based surfactant can be safely administered to patients with acute lung injury.

Richard and coworkers investigated the reliability of positron emission tomographic imaging in detecting the expression of genes delivered to the lungs by viral vectors. The study was conducted in normal rats and an enhanced mutant herpes simplex virus-1 thymidine kinase was used as the reporter gene. Rats were studied 3 days after the intratracheal administration of a replication-incompetent adenovirus containing a fusion gene for the mutant kinase and green fluorescent protein. The rats were injected with an imaging substance for the viral kinase, 9- (4-[¹⁸F]-fluoro-3-hydroxymethylbutyl)guanine; images were obtained 1 hour later. Measurements derived from imaging were linearly correlated with measures of thymidine kinase activity and green fluorescent protein levels in tissue (r² = 0.96). Imaging detected expression of thymidine kinase in 15 of 16 rats, even at low viral doses. Imaging for the viral kinase was correlated with in vitro assays for both kinase activity (r² = 0.48) and fluorescent protein (r² = 0.46). The authors conclude that positron emission tomographic imaging is a sensitive and quantitative method for noninvasive detection of pulmonary reporter gene expression.

To determine whether the individual response to inhaled nitric oxide changes over a prolonged course of therapy, Gerlach and coworkers did a prospective, randomized study in 40 patients with ARDS. Before treatment with inhaled nitric oxide, a dose–response curve revealed maximal improvement in Pa_O₂/FI_O₂ ratio at 10 ppm. After 4 days of continuous treatment (10 ppm), the dose–response curve to nitric oxide was shifted to the left with a peak response at 1 ppm. At higher doses (10 and 100 ppm), oxygenation deteriorated and several patients displayed no response to nitric oxide. This effect was not seen in the untreated control group. The authors conclude that patients with ARDS display enhanced sensitivity to nitric oxide within a few days of treatment, placing patients at risk of overdosing and worsening oxygenation.

Inhalation of nitric oxide has been advocated as a method to prevent ischemia–reperfusion injury after lung transplantation. Meade and coworkers did a randomized controlled trial of inhaled nitric oxide (22 ppm) versus placebo in 83 patients, initiated 10 minutes after reperfusion. PO₂/FI_O₂ was equivalent in the nitric oxide and placebo groups, 361 versus 351, on admission to the ICU. Severe hypoxemia, PO₂/FI_O₂ less than 150, taken as an index of severe reperfusion injury, was present in 14.6% of the nitric oxide group and 9.5% of the control group. The nitric oxide and placebo groups had equivalent times to first trial of spontaneous breathing (medians of 25 versus 27 hours), successful extubation (32 versus 34 hours), ICU discharge (3 days for both), and hospital discharge (27 versus 29 days). Five patients in the nitric oxide and six in the placebo group died in the hospital. The authors conclude that inhaled nitric oxide shortly after reperfusion does not alter clinical outcome in patients undergoing lung transplantation. An editorial commentary by Glanville accompanies this article.

To determine whether clinicians changed the setting of tidal volume between 1994 and 2001, Weinert and coworkers analyzed data on 398 patients with acute lung injury. In the first 5 years, tidal volume was 9.5 ml per kg (measured body weight). Tidal volume decreased between mid to late 1998; it was 8.9 ml per kg for the last 2 years of the study (the change in tidal volume occurred before initial release of results from the ARDS Network trial in 1999). A tidal volume of 6 ml per kg or less was used in 0.9% of patients. Between the first and third day of mechanical ventilation, the setting of tidal volume was decreased by only 33 ml. The authors conclude that clinicians started ventilating acute lung injury patients with lower tidal volumes in 1998 as compared with 1994, but the decrease in tidal volume was modest. An editorial commentary by Ricard accompanies this article.

Citations 1-7 of 7 total displayed.

Inhaled Nitric Oxide after Lung Transplantation: No More Cosmesis?

Allan R. Glanville
Am. J. Respir. Crit. Care Med. 167: 1463-1464. [Full text]

A Randomized Trial of Inhaled Nitric Oxide to Prevent Ischemia–Reperfusion Injury after Lung Transplantation

Maureen O. Meade, John T. Granton, Andrea Matte-Martyn, Karen McRae, Bruce Weaver, Paula Cripps, and Shaf H. Keshavjee
Am. J. Respir. Crit. Care Med. 167: 1483-1489. [Abstract] [Full text]

Treatment of Acute Respiratory Distress Syndrome with Recombinant Surfactant Protein C Surfactant

Roger G. Spragg, James F. Lewis, Wilhelm Wurst, Dietrich Häfner, Robert P. Baughman, Mark D. Wewers, and James J. Marsh
Am. J. Respir. Crit. Care Med. 167: 1562 -1566. First published online as doi:10.1164/rccm.200207-782OC [Abstract] [Full text]

Are We Really Reducing Tidal Volume—And Should We?

Jean-Damien Ricard
Am. J. Respir. Crit. Care Med. 167: 1297-1298. [Full text]

Impact of Randomized Trial Results on Acute Lung Injury Ventilator Therapy in Teaching Hospitals

Craig R. Weinert, Cynthia R. Gross, and William A. Marinelli
Am. J. Respir. Crit. Care Med. 167: 1304 -1309. First published online as doi:10.1164/rccm.200205-478OC [Abstract] [Full text]

Imaging Pulmonary Gene Expression with Positron Emission Tomography

Jean-Cristophe Richard, Zhaohui Zhou, Datta E. Ponde, Carmen S. Dence, Philip Factor, Paul N. Reynolds, Gary D. Luker, Vijay Sharma, Tom Ferkol, David Piwnica-Worms, and Daniel P. Schuster
Am. J. Respir. Crit. Care Med. 167: 1257 -1263. First published online as doi:10.1164/rccm.200210-1217OC [Abstract] [Full text]

Dose–Response Characteristics during Long-Term Inhalation of Nitric Oxide in Patients with Severe Acute Respiratory Distress Syndrome: A Prospective, Randomized, Controlled Study

Herwig Gerlach, Didier Keh, Alexander Semmerow, Thilo Busch, Klaus Lewandowski, Dirk M. Pappert, Rolf Rossaint, and Konrad J. Falke
Am. J. Respir. Crit. Care Med. 167: 1008-1015. [Abstract] [Full text]

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