Ann Thorac Surg 2005;79:713-715
© 2005 The Society of Thoracic Surgeons
Case report
Surviving Severe Acute Respiratory Distress Syndrome: Utility of Open-Lung Biopsy and Large Doses of Dexamethasone
Kedar S. Deshpande, MD*,a,
David W. Appel, MDb,
Margarita T. Camacho, MDc,
Kathryn E. Tanaka, MDd,
Vladimir Kvetan, MDe
a Divisions of Critical Care and Pulmonary Medicine, Department of Medicine, and Bronx, New York, USA
b USA
c Department of Cardiothoracic Surgery, Montefiore Medical Center for the Albert Einstein College of Medicine, Bronx, New York, USA
d Department of Pathology, Montefiore Medical Center for the Albert Einstein College of Medicine, Bronx, New York, USA
e Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New YorkUSA
Accepted for publication July 17, 2003.
* Address reprint requests to Dr Deshpande, Division of Critical Care Medicine, 111 E 210th St, Bronx, NY 10467, USA.
deshpandek{at}aol.com
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Abstract
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The etiology of acute respiratory distress syndrome is wide and mortality is extremely high. We describe a patient dying from severe acute respiratory distress syndrome who had a tremendous recovery after receiving dexamethasone (1 g daily). This patient required positive end-expiratory pressure (up to 18 mm/Hg) and fractional inspiratory oxygen (up to 100%). Thirty-six hours after the large dose of corticosteroids, the respiratory mechanics and oxygenation were acceptable for extubation. Acute respiratory distress syndrome was proven and other etiologies of respiratory failure were ruled out by a bedside open-lung biopsy. The biopsy proven acute respiratory distress syndrome dramatically resolved with this salvage therapy. High-dose usage of corticosteroids for acute respiratory distress syndrome has tremendous potential.
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Introduction
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Administering corticosteroids for the fibroproliferative acute respiratory distress syndrome improves respiratory mechanics [1, 2]. Meduri and colleagues [3] have now proven that there is a biochemical deficiency in glucocorticoid with acute respiratory distress syndrome. We describe a patient who had a tremendous recovery of respiratory failure after receiving dexamethasone (1 g intravenously daily) for the fibroproliferative phase of acute respiratory distress syndrome.
A 43-year-old woman, who was previously healthy, presented with a community acquired pneumonia that progressed to respiratory failure. A computed tomographic angiogram of the chest revealed right lower lobe consolidation and diffuse patchy infiltrate. No emboli were noted. Despite broad antibiotic coverage, the patient deteriorated and was admitted to the intensive care unit 6 days after admission for endotracheal intubation with vasopressor support.
The patient was ventilated with low volumes and positive end-expiratory pressure (as great as 18 mm/Hg) with heavy sedation to achieve a plateau pressure less than 35 mm Hg. The fractional inspiratory oxygen ranged from 80% to 100%. Studies for infectious causes were negative (Table 1), as were serologic studies for connective tissue disorders and vasculitis. The hemodynamic profile was consistent with hyperdynamic vasodilation with adequate volume resuscitation and acute respiratory distress syndrome.
A bedside open-lung biopsy was performed in the intensive care unit 9 days after admission. Histologic examination (Fig 1) . revealed changes of both acute and organizing diffuse alveolar damage with interstitial edema, hyaline membranes, and preserved alveolar architecture. Focal pneumocyte hyperplasia, remnants of hyaline membranes, and organizing thrombi in small-sized and medium-sized vessels were also noted. These findings are that of the organizing stage of diffuse alveolar damage. There was no evidence of pulmonary edema, pulmonary eosinophilia, granulomas, or viral inclusions. Stains for fungus, acid fast bacilli, and Pneumocystis carinii pneumonia were negative.
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Fig 1. Low-magnification photomicrograph of organizing diffuse alveolar damage showing thickened alveolar septa. Inset: Higher magnification of thickened septa showing fibroblasts and hyaline membrane remnants.
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The patient had the fibroproliferative phase of acute respiratory distress syndrome based on clinical presentation and pathologic findings. The recommended dose of methylprednisolone (100 mg intravenously every 6 hours) was started immediately, but 24 hours later, the respiratory status and chest roentgenograms remained unchanged. Given the difficulties in oxygenating the patient and believing that the histologic preserved lung architecture was good evidence that the patient could recover significantly, the corticosteroids were empirically increased to dexamethasone (1 g intravenously daily) as salvage therapy. The following day, the chest roentgenogram showed remarkable improvement, the partial pressure of arterial oxygen and fractional inspiratory oxygen ratio increased from 65 to 237, and the overall lung injury score decreased from 12 to 7. Her oxygen status and respiratory mechanics permitted extubation 36 hours after initiating dexamethasone. The fluid balance remained even through the intensive care unit stay. The corticosteroids were tapered and discontinued gradually after 2 weeks, and the patient was discharged home.
The patient was seen in the clinic 2 weeks after discharge. She was able to return to work and was fully active. The pulmonary function tests obtained 1 month later showed only mild restrictive abnormality.
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Comment
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Often patients survive initial catastrophic events, such as sepsis and trauma, only to die from respiratory failure and acute respiratory distress syndrome. When initiated in a timely manner, corticosteroids have shown to reverse respiratory failure to the point at which patients are liberated from ventilatory support [1, 2]. The earliest improvement in pulmonary function reported after treatment with recommended doses of corticosteroids with acute respiratory distress syndrome is approximately 7 days [4].
The three phases of acute respiratory distress syndrome are the exudative phase, the fibroprofilerative phase, and the fibrotic phase. Catastrophic events release cytokines resulting in a generalized systemic inflammatory response syndrome. Capillary permeability increases with deposition of interstitial protein resulting in noncardiogenic interstitial pulmonary edema [5]. This initial insult is known as the exudative phase of acute respiratory distress syndrome. At times, even when the inciting event is treated appropriately and the systemic inflammatory response syndrome resolves, the lungs continue to recruit inflammatory cells and place collagen in the pulmonary parenchyma. This process known as the fibroproliferative phase of acute respiratory distress syndrome occurs approximately 10 to 14 days after the onset of respiratory failure; initiation of corticosteroids in this instance have been shown to reverse respiratory failure [2, 4]. At times, the fibroproliferative phase of acute respiratory distress syndrome progresses to the fibrotic phase.
A recent review by Luce [1] also shows that timing of corticosteroids is paramount. Initiation of corticosteroids too early in the course of systemic inflammatory response syndrome and acute respiratory distress syndrome is not helpful and is potentially harmful. However, delaying treatment can result in progression of fibrosis.
The dose of corticosteroid used in our patient was greater than 10x the traditional dose of methylprednisolone (2 to 3 mg/kg/d) (ie, dexamethasone, 1 g = methylprednisolone, 5.3 g). Studies involving spinal cord injury have demonstrated that short courses of very high corticosteroid doses are safe [6]. Although studies have shown that using high doses of corticosteroids in acute respiratory distress syndrome (methylprednisolone, 30 mg/kg every 6 hours) increases mortality, these doses were used in the early stages of systemic inflammatory response syndrome to prevent acute respiratory distress syndrome rather than to treat acute respiratory distress syndrome [7]. The higher mortality likely reflects the patient population and the timing of the corticosteroids rather than the dosage.
Lung biopsy specimens from patients with acute respiratory distress syndrome have abundant inflammatory cells and increased corticosteroid receptors [2]. As long as the pulmonary architecture is intact, initiating corticosteroids can stop fibroproliferation and improve gas exchange, potentially to the point at which patients can be liberated from mechanical ventilation. Given the glucocorticoid deficiency [1] and increased corticosteroid receptors in acute respiratory distress syndrome, we postulate that the dramatic response to the large dose of corticosteroids in our patient was likely a dose effect. Furthermore, Grunze and colleagues [8] showed that dexamethasone has greater anti-inflammatory properties and improved lung compliance compared with methylprednisolone. Thus, the dramatic response of our patient could have been due to the dose of dexamethasone administered or due to its unique properties, or both.
Given the clinical presentation, the open-lung biopsy proved our patient had the fibroproliferative phase of acute respiratory distress syndrome and excluded other causes of respiratory failure. Furthermore, the open-lung biopsy provided us with evidence of preserved alveolar architecture. With this information, we decided to treat this dying patient who did not respond to conventional doses of corticosteroids with very large doses of dexamethasone as salvage therapy. After one dose of dexamethasone (1 g), the infiltrates on the chest roentgenogram significantly improved and the partial pressure of arterial oxygen and fractional inspiratory oxygen ratio increased by 172 points in 24 hours. The biopsy proven fibroproliferative phase of acute respiratory distress syndrome had a dramatic response to the high dose of corticosteroid.
In conclusion, the remarkable aspect of this case was the unprecedented rapid resolution of the severe respiratory failure from the fibroproliferative phase of acute respiratory distress syndrome after treatment with daily dexamethasone (1 g) intravenously. Because prolonged respiratory failure increases the risk of multiorgan failure and death, the fast reversal of respiratory failure was the decisive event that prevented this patient's mortality. Further studies are required before such doses of corticosteroids are widely recommended. Large doses of corticosteroids in acute respiratory distress syndrome hold great potential.
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References
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- Luce J. Corticosteroids in ARDS: an evidence based review. Crit Care Clin. 2002;18(1):79–89[Medline]
- Meduri GU, Chinn AJ, Leeper KV, et al. Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS. Chest. 1994;105:1516–1527[Abstract/Free Full Text]
- Meduri GU, Tolley EA, Chrousos GP, et al. Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome. Evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med 2002(165):983–91
- Meduri GU, Belenchia JM, Estes RJ, et al. Fibroproliferative phase of ARDS: clinical findings and effect of corticosteroids. Chest. 1991;100(4):943–952[Abstract/Free Full Text]
- Williams TJ, Yarwood H. Effects of glucocorticosteroids on microvascular permeability. Am Rev Respir Dis. 1990;141:S39–43[Medline]
- Bracken MB, Shepard MJ, Collins WF, et al. The randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. N Engl J Med. 1990;322(20):1405–1411[Abstract]
- Luce JM, Montgomery AB, Marks JD, et al. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis. 1988;138:62–68[Medline]
- Grunze MF, Parkinson D, Sulavik SB, et al. Effect of corticosteroids on lung volume-pressure curves in bleomycin-induced lung injury in the rat. Exp Lung Res. 1988;14(2):183–195[Medline]
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Abstract
Introduction
