ARDS associated with tumor lysis syndrome in a patient with non-Hodgkin''s lymphoma

ARDS developed in association with tumor lysis syndrome (TLS) in a patient with non-Hodgkin's lymphoma. Although a number of life-threatening complications have been noted to occur following TLS, this appears to be the first report of ARDS developing in association with TLS.     

CD11b/CD18 expression, adherence, and chemotaxis of granulocyte in adult respiratory distress syndrome

The accumulation of granulocytes in the pulmonary microvasculature is generally thought a cardinal event in the pathology of adult respiratory distress syndrome (ARDS). However, the mechanism by which granulocytes are sequestered in the pulmonary vascular bed remains largely unknown. Because the CD11b/CD18 membrane receptors mediate various adhesion-dependent functions, their expression was investigated in granulocytes from patients during the course of ARDS development in relation to adherence and chemotaxis. CD11b expression of ARDS resting granulocytes was increased within 24 h of ARDS onset by a factor of two in comparison with control patients (p < 0.05) and remained significantly increased 72 to 120 h later. In contrast, the stimulated expression was significantly decreased only within 24 h of ARDS onset. Adherence was not modified within 8 h of the onset of ARDS, but was increased at Days 1, 3, and 5. The time course of granulocyte chemotaxis shows a decreased chemotaxis capacity during the first 3 d of ARDS, followed by normalization at Day 5. The dynamic changes observed in the various functions studied indicate a possible relationship between the modulation of the CD11b expression and a hyperadhesive state of granulocytes in ARDS. These sticky granulocytes may potentially contribute to the microvascular injury.     

Gene rearrangement and truncated mRNA in cell lines with 11q23 translocation

This study was done to evaluate the diagnostic accuracy of bedside chest radiography for pneumonia, adult respiratory distress syndrome (ARDS), or both in patients receiving mechanical ventilation. The series consisted of 40 patients; diagnostic accuracy was defined as the area under the receiver operating characteristic curve. Overall diagnostic accuracy for ARDS was 0.84. Overall diagnostic accuracy for pneumonia was 0.52. Review of previous radiographs and knowledge of clinical data did not enhance diagnostic accuracy for ARDS or pneumonia. Diagnostic accuracy for pneumonia was minimally reduced when ARDS was present. There was an increase in false-negative results because the diffuse areas of increased opacity in ARDS obscured the radiographic features of pneumonia. The authors conclude that chest radiography is of limited value for the diagnosis of pneumonia in patients receiving mechanical ventilation. The high false-negative and false-positive ratings for pneumonia resulted in a low diagnostic accuracy. The high diagnostic accuracy for ARDS was primarily due to the well-defined radiographic appearance of ARDS and few false-positive ratings.     

Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome

The effects of bacterial endotoxin (lipopolysaccharide, LPS) are amplified by lipopolysaccharide binding protein (LBP) and CD14, resulting in cellular activation at very low concentrations of LPS. To investigate the importance of this pathway in acute lung injury, we measured LPS, LBP, and soluble CD14 (sCD14) in the bronchoalveolar lavage fluid (BAL) of 82 patients with acute respiratory distress syndrome (ARDS). LBP and sCD14 increased markedly in BAL of patients with ARDS. sCD14 and LBP each were strongly related to BAL total protein and polymorphonuclear neutrophil (PMN) concentration, whereas LPS concentration was not. Multivariate analyses showed sCD14 to be strongly related to BAL total protein, even after controlling for LPS and LBP concentrations. sCD14 was strongly and independently related to PMN concentration, after controlling for BAL LPS, LBP, and interleukin-8 (IL-8). The BAL LPS concentration was not strongly related to either BAL total protein or BAL PMN. The BAL sCD14 and LBP values were similar in all subgroups of patients with ARDS, and were not related to survival. The serum LBP and sCD14 were elevated in ARDS, but were not related to BAL total protein, LBP, sCD14, PMN, or clinical outcome. Thus, LBP and sCD14 reach high concentrations in the lungs of patients with ARDS, and BAL sCD14 is strongly related to two major indices of lung inflammation: total protein and PMN concentration. CD14-dependent mechanisms may contribute to lung inflammation in ARDS.     

Current aspects of acute respiratory distress syndrome in children

Acute respiratory distress syndrome (ARDS) is a frequent condition in pediatric intensive care units. The mortality remains high despite advances in conventional mechanical ventilation and aetiological treatment. Several animal studies have documented lung injury during mechanical ventilation with high tidal volume, and clinical investigations have shown that in human ARDS, most ventilation is distributed to the small areas of remaining aerated lung resulting in overdistension of these areas and lung injury ("baby lung" theory). Nevertheless the usefulness of extrapulmonary gas exchange remains much debated. New ventilatory strategies have been developed in order to reduce ventilator-induced lung injury and to improve systemic oxygenation but multicentric randomized clinical trials are needed before these strategies can be validated.     

Extracorporeal membrane oxygenation for nonneonatal pulmonary and multiple-organ failure

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is an accepted therapy for neonatal pulmonary failure, but its use in older children has been controversial. METHODS: Over 13 years, 55 children (ages, 3 months to 16 years) were treated with venoarterial or venovenous ECMO. The diagnoses were viral, bacterial, or fungal pneumonia (24 patients); hydrocarbon or gastric aspiration (n = 10); adult respiratory distress syndrome (ARDS), sepsis, near drowning (n = 15); pulmonary contusion (n = 2); airway obstruction (n = 3); pulmonary artery foreign body (n = 1). Pre-ECMO blood gas ranges (and means) were PO2, 21 to 100 (n = 44); PCO2, 23 to 125 (n = 72); pH, 6.81 to 7.55 (n = 7.11). RESULTS: All patients received inotropes, and 38 required dialysis or hemofiltration. ECMO was used for 20 to 613 hours (mean, 196 hours). Patient complications included cannulation site hemorrhage (n = 40), renal failure (n = 10), seizures (n = 8), stroke (n = 3), and cerebral hemorrhage (n = 2). Twenty-five patients (45%) survived ECMO, with 21 long-term survivors (10 pneumonia, five aspiration, five ARDS, one pulmonary contusion), five of whom have mild to moderate neurological deficit. Patients with combinations of pulmonary, cardiac, and renal failure, or sepsis did not survive. CONCLUSIONS: ECMO is an invasive technique that can be life saving in the child with isolated respiratory failure, but its usefulness in children with multiorgan failure is less certain.     

Hantavirus pulmonary syndrome: epidemiology, prevention, and case presentation of a new viral strain

Hantavirus pulmonary syndrome (HPS) is a viral infection from a new strain of Hantavirus. The Hantavirus was first discovered in North America in 1993 after an outbreak of fatal illness on a Navajo Indian reservation in New Mexico. Since then, 122 cases of HPS (with a high mortality rate of more than 50%) have been reported in 23 states, with the highest prevalence in the Four Corners area. The reservoir for Hantavirus is small rodents, mostly field mice, vole, and chipmunks. It is transmitted through inhalation of airborne virus from dry rodent excreta and saliva. A North American strain of Hantavirus, named ain nombre virus (SNV), primarily affects the lungs, causing rapid accumulation of fluids and leading to noncardiogenic pulmonary edema, pleural effusion, and acute respiratory distress syndrome (ARDS). In the prodromal stage, HPS presents with flu-like symptoms, nausea, vomiting, and gastrointestinal pain and is often mistaken on the first visit for other infectious diseases or gastroenteritis. In the second acute stage, rapid respiratory deterioration begins: HPS is often misdiagnosed for pneumonia, idiopathic ARDS, and pulmonary edema. HPS treatment with an experimental antiviral intravenous drug, ribavirin, is under investigation. Practitioners must possess through clinical knowledge on the diagnoses, pathology, treatment, and course of the disease to reduce the mortality and morbidity rate of this rare but serious infection. A case report based on a recent HPS death in New York State on Long island in April 1995 is presented.     

Intraoperative maintenance of tissue perfusion prevents ARDS. Adult Respiratory Distress Syndrome

Patients undergoing prolonged, complex oncological surgery are at increased risk of developing the adult respiratory distress syndrome (ARDS) and other organ failures. Our hypothesis is that maintaining adequate tissue perfusion and oxygenation may prevent tissue hypoxia and acidosis in pulmonary, peripheral, and splanchnic microcirculations. Experimental evidence suggests that the hypoxic, acidotic endothelium stimulates the release of cytokines, kinins, and other mediators. We developed and tested an intraoperative protocol for surgical patients likely to develop ARDS and organ dysfunction; the protocol focuses on the intraoperative period but is not limited to this time. Nitroglycerin and fluids were used to maintain tissue perfusion and prevent tissue hypoxia as reflected by transcutaneous oxygen tension values. In 155 high-risk patients, none developed ARDS. We conclude that maintenance of tissue perfusion and oxygenation in high-risk surgical patients decreases the incidence of ARDS.     

Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure

OBJECTIVE: This study investigates the course of serum cytokine levels in patients with multiple trauma, patients with a ruptured abdominal aortic aneurysm (AAA), and patients undergoing elective AAA repair and the relationship of these cytokines to the development of adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Severe tissue trauma, hemorrhagic shock, and ischemia-reperfusion injury are pathophysiologic mechanisms that may result in an excessive uncontrolled activation of inflammatory cells and mediators. This inflammatory response is thought to play a key role in the development of (remote) cell and organ dysfunction, which is the basis of ARDS and MOF. METHODS: The study concerns 28 patients with multiple trauma, 20 patients admitted in shock because of a ruptured AAA, and 18 patients undergoing elective AAA repair. Arterial blood was serially sampled from admission (or at the start of elective operation) to day 13 in the intensive care unit, and the serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 were determined. RESULTS: Twenty-two patients died, 15 within 48 hours and 7 after several weeks, as a result of ARDS/MOF. At hospital admission and after 6 hours, these nonsurvivors had significantly higher plasma TNF-alpha and IL-1 beta levels than did the survivors. At the same measuring points, TNF-alpha and IL-1 beta were significantly more elevated in patients with ruptured AAA than in traumatized patients. However, IL-6 was significantly higher in the traumatized patients. In 10 patients, ARDS/MOF developed, and 41 had an uncomplicated course in this respect. Those with ARDS/MOF exhibited significantly different cytokine patterns in the early postinjury phase. TNF-alpha and IL-1 beta levels were higher mainly on the first day of admission; IL-6 concentrations were significantly elevated in patients with ARDS/MOF from the second day onward. The latter cytokine showed a good correlation with the daily MOF score during the whole 2-week observation period. CONCLUSIONS: In the early postinjury phase, higher concentrations of these cytokines are associated, not only with an increased mortality rate, but also with an increased risk for subsequent ARDS and MOF. These data therefore support the concept that these syndromes are caused by an overwhelming autodestructive inflammatory response.     

Has high-frequency ventilation been inappropriately discarded in adult acute respiratory distress syndrome?

OBJECTIVES: To review the basic physiologic principles that support the role for high-frequency ventilation (HFV) in acutely lung-injured patients, to critically assess clinical trial data in this area, and discuss why a metasummary is not feasible and a large-scale clinical trial is needed. DATA SOURCES: We searched a computerized database (MEDLINE) from 1976 to January 1997 using the text words "high-frequency ventilation" and "acute respiratory distress syndrome" to retrieve all relevant candidate articles. STUDY SELECTION: We retrieved all English language clinical studies conducted in tertiary care centers that employed HFV in adult acute respiratory distress syndrome (ARDS) patients. DATA EXTRACTION: Only prospective, randomized trials, cohort/case-control studies, and case series evaluating HFV vs. conventional mechanical ventilation in adult ARDS patients were included. DATA SYNTHESIS: We independently screened 3,166 articles on ARDS and 494 papers on HFV in our computer search. We checked reference lists and contacted experts in the field of mechanical ventilation in ARDS to ensure that no relevant studies had been missed. Only four articles met our inclusion criteria and were evaluated in detail. CONCLUSIONS: Current clinical studies are statistically under-powered and a metasummary is not feasible because of study quality, as well as lack of similar clinical end points and measures of magnitude of benefit. A large, multicenter trial should be initiated to define the role of HFV in the treatment of adult ARDS.     

The role of the host defence response in the progression and outcome of ARDS: pathophysiological correlations and response to glucocorticoid treatment

The host defence response (HDR) to insults is similar regardless of the tissue involved and consists of an interactive network of simultaneously activated pathways that act in synergy to increase the host's chance of survival. Among this cascade of integrated pathways, three aspects of the HDR, inflammation, coagulation and tissue repair, are analysed separately to explain the histological and physiological changes occurring at the tissue level in unresolving acute respiratory distress syndrome (ARDS). Cellular responses in HDR are regulated by a complex interaction among cytokines, and cytokines have concentration-dependent biological effects. The degree of initial HDR may determine the progression of ARDS. On Day 1 of mechanical ventilation and over time, nonsurvivors of ARDS have significantly higher plasma and bronchoalveolar lavage inflammatory cytokine levels than survivors. In the absence of inhibitory signals, the continued production of HDR mediators prevents effective restoration of lung anatomy and function by sustaining inflammation with tissue injury, intra- and extravascular coagulation and proliferation of mesenchymal cells (fibroproliferation) with deposition of extracellular matrix resulting in fibrosis. Glucocorticoids inhibit the HDR cascade at virtually all levels; their gradual and generalized suppressive influence protects the host from overshooting. In patients with exaggerated HDR, however, cytokine elevation may cause a concentration-dependent resistance to glucocorticoids by reducing glucocorticoid receptor binding affinity. Recent clinical and experimental studies have shown that effective containment of the HDR in unresolving ARDS may be achieved only if glucocorticoid administration is prolonged. A double-blind randomized study is in progress to evaluate the role of prolonged glucocorticoid treatment in unresolving ARDS.     

Adult respiratory failure

Pulmonary complications following thoracic surgery are common and associated with significant morbidity and mortality. In particular, acute respiratory distress syndrome (ARDS) can occur postoperatively or after trauma. This syndrome, when complicated by multisystem organ failure, often leads to a poor outcome. This article describes the etiology and pathophysiology of ARDS and evaluates recent advances in pharmacological and nonpharmacological therapies. In addition, newer modalities of mechanical ventilatory support are reviewed.     

Post-traumatic ARDS--a potential indication for lung transplantation?

Posttraumatic adult respiratory distress syndrome (ARDS) still involves significant mortality, despite progress in management concepts. Current therapeutic strategies are briefly described, including kinetic therapy, high-frequency jet ventilation and extracorporeal membrane oxygenation. In addition, a spectacular case of the first successful lung transplantation for posttraumatic ARDS after failed ECMO (extracorporeal membrane oxygenation) support is reported. This young man with severe posttraumatic ARDS developed a potentially lethal bilateral pulmonary hemorrhage under treatment with ECMO, and on the basis of this bilateral pulmonary transplantation was considered to be indicated. The patient is alive and well 2 years after the procedure.     

Bilateral pulmonary infiltrations in patients admitted to an intensive care unit

Diffuse pulmonary infiltrates are commonly found in hypoxic respiratory failure. We have reviewed 16 patients admitted to our medical intensive care unit over a period of 21 months, of whom seven died in hospital. Only patients requiring ventilatory support (CPAP or mechanical ventilation) for respiratory failure due to non-cardiogenic causes were included. All patients met the criteria for the diagnosis of ARDS. Three patients suffered from Wegener's granulomatosis, three from Pneumocystis carinii pneumonia, three from bacterial pneumonia, and two from pneumonia. Staphylococcal septicemia, SLE, sarcoidosis, cancer-associated hemolytic-uremic syndrome and ARDS of unknown etiology were each found in one patient. We discuss diagnosis and treatment of such patients on the basis of our experience.     

Pharmacologic adjuncts to mechanical ventilation in acute respiratory distress syndrome

This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole, antioxidants, corticosteroids, surfactant, ketanserin, pentoxifylline, bronchodilators, and almitrine in ARDS. Current animal data and proposed mechanics which may foster future pharmacologic therapies are also examined.     

Multi-organ failure syndrome. Pathophysiology, prevention, treatment

MOFS Multi-Organ-Failure-Syndrome has not been recognized until past 10 to 20 years. There are many different causes that may lead to MOFS. Recently it has become clear that MOFS is the clinical endstage of the systemic hypermetabolic response to injury that is heralded by acute lung injury and followed by hepatic and renal failure and often by death. The lung injury may range from relatively slight increase of pulmonary small vessels leakage to the adult respiratory distress syndrome (ARDS). In the first part of the following paper there are presented two clinical cases resulted in MOFS. Pathophysiology, current therapy and prophylaxis of MOFS are reviewed in the second part.     

Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice

PURPOSE: To determine the diagnostic accuracy of computed tomography (CT) for pneumonia in patients with adult respiratory distress syndrome (ARDS). MATERIALS AND METHODS: CT scans were obtained within 1 week of bronchoscopic sampling in 31 patients receiving mechanical ventilation for ARDS for more than 48 hours. Of 11 patients with pneumonia, five developed symptoms less than 11 days after the onset of ARDS (early ARDS). CT scans were rated for pneumonia independently by four radiologists who were unaware of the clinical diagnosis. Diagnostic accuracy was defined by means of the area under the receiver operating characteristic curve, or A2. RESULTS: Diagnostic accuracy for pneumonia was fair (A2 = 0.69 +/- 0.04 [standard error]) owing to 70% true-negative ratings (vs 59% true-positive ratings). The generalizability coefficient was good (0.79). No single CT finding was significantly different for the presence of pneumonia. Nondependent opacities predominated in 10 (91%) of 11 patients with pneumonia and 12 (60%) of 20 without pneumonia. Nondependent opacities predominated in nine (56%) of 16 patients with early ARDS and 13 (87%) of 15 with late ARDS. CONCLUSION: CT has fair diagnostic accuracy for ventilator-associated pneumonia in patients with ARDS owing primarily to identification of patients without pneumonia. No single CT sign was significantly different for pneumonia, but dependent atelectasis was more common in patients with early ARDS without pneumonia.     

Gastroschisis: a radiological and clinical review

The paediatric patient we are describing suffered a scald injury covering 83 per cent of the total body surface area (TBSA). This injury was complicated by Klebsiella pneumoniae septicaemia resulting in multiorgan failure (MOF). Acute respiratory distress syndrome (ARDS), gastrointestinal insufficiency, hepathopathy and wound conversion to full thickness posed the main problems. The boy was ventilated with pressure-controlled mechanical ventilation. The concept of permissive hypercapnia (PHC) resulted in a complete resolution of ARDS within 4 weeks. From our experience, further lung injury among infants and children suffering from severe ARDS can be avoided by using controlled mechanical hypoventilation. It is a simple and safe technique that allows adequate oxygenation.     

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.     

High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.