Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group.

OBJECTIVE: To evaluate the safety and efficacy of an intravenous liposomal dispersion of prostaglandin E1 as TLC C-53 in the treatment of patients with acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled, phase III clinical trial. SETTING: Forty-seven community and university-affiliated hospitals in the United States. PATIENTS: A total of 350 patients with ARDS were enrolled in this clinical trial. INTERVENTION: Patients were prospectively randomized in a 1:1 ratio to receive either liposomal prostaglandin E1 or placebo. The study drug was infused intravenously for 60 mins every 6 hrs for 7 days starting with a dosage of 0.15 microg/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 microg/kg/hr) was attained or intolerance to further increases developed. Patients received standard aggressive medical/surgical care during the infusion period. OUTCOME MEASURES: The primary outcome measure was the time it took to wean the patient from the ventilator. Secondary end points included time to improvement of the PaO2/FIO2 ratio (defined as first PaO2/FIO2 > 300 mm Hg), day 28 mortality, ventilator dependence at day 8, changes in PaO2/FIO2, incidence of and time to development/resolution of organ failure other than ARDS. RESULTS: A total of 348 patients could be evaluated for efficacy. The distribution of variables at baseline describing gender, lung injury scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS or from institution of mechanical ventilation to the first dose of study drug was similar among patients in the liposomal prostaglandin E1 (n = 177) and the placebo (n = 171) treatment arms. There was no significant difference in the number of days to the discontinuation of ventilation in the liposomal prostaglandin E1 group compared with the placebo group (median number of days to off mechanical ventilation, 16.9 in patients receiving liposomal prostaglandin E1 and 19.6 in those administered placebo; p = .94). Similarly, mortality at day 28 was not significantly different in the two groups (day 28 mortality, 57 of 176 (32%) in the liposomal prostaglandin E1 group and 50 of 170 (29%) in patients receiving placebo; p = .55). In contrast, treatment with liposomal prostaglandin E1 was associated with a significantly shorter time to reach a PaO2/FIO2 ratio of >300 mm Hg (median number of days to reaching a PaO2/FIO2 ratio >300 mm Hg: 9.8 days in the liposomal prostaglandin E1 group and 13.7 days in patients receiving the placebo; p = .02). Among the subgroups examined, time to off mechanical ventilation was significantly reduced in patients who received at least 85% of a full dose (i.e., > 45.9 microg/kg) of liposomal prostaglandin E1 (median number of days to discontinuation of ventilation, 10.3 in the liposomal prostaglandin E1 group and 16.3 days in patients receiving placebo; p = .05). The overall incidence of serious adverse events was not significantly different in the liposomal prostaglandin E1 (40%) or placebo-treated (37%) groups. Drug-related adverse events of all kinds were reported in 69% of the patients receiving liposomal prostaglandin E1 compared with 33% of the placebo group, with hypotension and hypoxia (occurring in 52% and 24% of the liposomal prostaglandin E1-treated patients, respectively, and 17% and 5% of the placebo-treated patients, respectively) being noted most frequently. CONCLUSIONS: In the intent-to-treat population of patients with ARDS, treatment with liposomal prostaglandin E1 accelerated improvement in indexes of oxygenation but did not decrease the duration of mechanical ventilation and did not improve day 28 survival.

Significant tracheal obstruction causing failure to wean in patients requiring prolonged mechanical ventilation: a forgotten complication of long-term mechanical ventilation.

INTRODUCTION: Modern low-pressure, high-volume cuffed tracheotomy tubes have been shown to decrease tracheal injury. However, injury still occurs in patients requiring prolonged mechanical ventilation and prevents weaning, delays decannulation, prolongs hospitalization, and may totally obstruct the airway. We describe 37 patients, including the first reported case of failure to wean due to tracheal obstruction. METHODS: Over a 3-year period, from September 1994 to August 1997, the hospital records of 37 patients requiring prolonged mechanical ventilation (> 4 weeks) and found to have tracheal obstruction were reviewed retrospectively. They were a subgroup of 756 patients admitted to hospitals during the same period. The average endotracheal/tracheostomy cannulation time was 3 weeks/12 weeks (range 2 to 4 weeks/8 to 14 weeks). Average age was 76 years (range, 34 to 81). Underlying diseases included COPD, postcoronary artery bypass graft surgery, postpneumonectomy, severe pneumonia, acute lung injury, and ischemic heart disease. RESULTS: All 37 patients who initially failed to wean had difficulty in breathing and developed intermittent high peak airway pressures either early or during the weaning process or just on being ventilated. The insertion of a longer tracheal tube bypassed the obstruction, reestablished the airway, decreased peak airway pressures, and allowed the patient to breathe more easily. The obstruction was confirmed on bronchoscopy. Treatment consisted of either placement of a longer tracheal tube (34 of 37 patients) or placement of a tracheal stent. All but two of the patients (5.4%) were able to be weaned within a week. The two patients who still failed to be weaned were subsequently diagnosed as having amyotrophic lateral sclerosis. CONCLUSION: Tracheal obstruction in patients requiring prolonged mechanical ventilation prevented weaning. Reestablishment of the airway with a longer tracheal tube or tracheal stent allowed most of the patients to be weaned.

The initial pulmonary evaluation of the immunocompromised patient.

Practical approaches to the initial evaluation of solid organ transplant patients, BMT patients, and HIV-infected patients with pulmonary disease are summarized in Figures 2, 3, and 4. These algorithms are meant to be used as guidelines for the clinician. The clinical setting will ultimately determine the extent and speed of the evaluation. Patients who are recipients of solid organ transplants and have pulmonary symptoms may have focal or diffuse changes or may have normal chest radiographs. In all these groups, sputum is obtained by expectation. If a pathogen is found in any of the groups, it is treated. When no pathogen is found on sputum examination in patients with focal disease, empiric antibiotic therapy is given. If the patients do not improve on the empiric antibiotics, then bronchoscopy is performed. Some centers proceed directly to bronchoscopy before antibiotics are started in the hope of directing antibiotic therapy. Patients who have a normal CXR or diffuse infiltrates and no identified pathogen on examination of sputum undergo bronchoscopy, and the protocol is followed until a diagnosis is made (see Fig. 2). Patients who have received a BMT and who present with pulmonary symptoms are treated as shown in Figure 3. The CXR will reveal if the infiltrate is focal or diffuse. Those with focal infiltrates are treated with broad-spectrum antibiotics for 48 to 72 hours. If the symptoms and signs do not show some resolution, then bronchoscopy is usually performed. The effect of diffuse infiltrates in BMT patients depends to a large extent how far along in recovery from the transplant the patient is when they develop the infiltrates. During the first 30 days posttransplant, pulmonary edema commonly occurs, and the infiltrates may resolve with diuresis. If the patient is not clinically fluid overloaded or they do not respond to the diuretic therapy, then bronchoscopy with BAL is indicated. Finally, many HIV-infected patients may present with pulmonary symptoms. They may have a normal CXR or a diffuse or focal pattern (Fig. 4). All patients are subjected to sputum induction to identify a pathogen. If one is identified, it is treated. Should the patient not respond to treatment adequately or a pulmonary pathogen is not found, then bronchoscopy with BAL, protected specimen brush, or a transbronchial biopsy is attempted. The above schema is a general guideline to the initial evaluation of pulmonary disorders in the ICP. The respiratory abnormality is found in most of the cases if these algorithms are closely followed. If the patient does not improve or deteriorates further, additional diagnostic procedures such as video-assisted thorascopic lung biopsy or CT-directed transthoracic needle biopsy may be needed.

Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group.

BACKGROUND: Despite the availability of potent antibiotics and intensive care, mortality rates from septic shock are 40-70%. We assessed the safety and efficacy of murine monoclonal antibody to human tumour necrosis factor alpha (TNF alpha MAb) in the treatment of septic shock. METHODS: In a randomised, multicentre, double-blind, placebo-controlled clinical trial in 105 hospitals in the USA and Canada, we randomly assigned 1879 patients a single infusion of 7.5 mg/kg TNF alpha MAb (n=949) or placebo (0.25% human serum albumin n=930). Our main outcome measurement was the rate of all-cause mortality at 28 days. FINDINGS: 382 (40.3%) of 948 patients who received TNF alpha MAb and 398 (42.8%) of 930 who received placebo had died at 28 days (95% CI -0.02 to 0.07, p=0.27). We found no association between therapy with TNF alpha MAb and increased rapidity in reversal of initial shock or prevention of subsequent shock. Similarly, baseline plasma interleukin-6 concentrations of more than 1000 pg/mL or detectable circulating TNF concentrations were not associated with improvement in survival after TNF alpha MAb therapy. Coagulopathy but not other organ or system failures, was significantly decreased in the TNF alpha MAb group compared with placebo (day 7, p<0.001; day 28, p=0.005). Serious adverse events were reported in 55.2% of patients given placebo and 54.1% in the TNF alpha MAb group. INTERPRETATION: We did not find an improvement in survival after septic shock with TNF alpha MAb. Therapy not solely dependent on TNF alpha blockade may be required to improve survival.

Tracheostomy tube occlusion protocol predicts significant tracheal obstruction to air flow in patients requiring prolonged mechanical ventilation.

OBJECTIVE: This study was undertaken to test the hypothesis that a tracheal tube occlusion protocol predicts clinically important obstruction to air flow in patients requiring prolonged mechanical ventilation, making routine bronchoscopy unnecessary. DESIGN: A prospective evaluation of 75 patients who were clinically ready to be decannulated. All patients underwent the tracheal tube occlusion protocol followed by bronchoscopy. SETTING: Three hospitals affiliated with a college of medicine. PATIENTS: Over a 24-month period, 52 males and 23 females were enrolled in the study. Mean age was 55 yrs (range 25 to 85). Mean endotracheal/tracheostomy time was 2.4/8.9 wks (range 1 to 4/5 to 14). All patients were mechanically ventilated for at least 4 wks and were successfully weaned from the mechanical ventilator for at least 48 hrs. During spontaneous breathing, these data were observed: minute ventilation of < 10 L/min; resting respiratory rate of < 18 breaths/min; and arterial oxygen saturation of > 90% on 40% oxygen tracheal collar mask. The tracheal tube occlusion protocol consisted of deflating the cuff on the fenestrated tracheal tube and occluding the tube. INTERVENTIONS: Patients who developed respiratory distress when the tracheal tube was occluded were deemed to have failed the protocol. At bronchoscopy, the patients were asked to cough and hyperventilate in an attempt to forcibly reduce the cross-sectional area of the trachea. A sustained, subjectively assessed decrease of > or = 50% of the effective cross-sectional area of the trachea was considered to be an indication for intervention. MEASUREMENTS AND MAIN RESULTS: Sixty-three (84%) of 75 patients tolerated the tracheal tube occlusion protocol. Twelve (16%) of 75 patients developed signs of respiratory distress and showed decreased oxygen saturation values necessitating uncapping of the tracheal tube. All patients had some degree of tracheal injury. However, those patients who failed to tolerate the tracheal tube occlusion protocol had clinically important tracheal obstruction to air flow. CONCLUSION: A tracheal tube occlusion protocol can predict clinically important obstruction to air flow after prolonged mechanical ventilation.

Left hilar mass in a 62-year-old man: severe pulmonary valvular stenosis with a poststenotic aneurysm.

We describe a patient who had a left hilar mass initially diagnosed as probable bronchogenic carcinoma. When a paradoxic arterial embolus led to further investigation, the hilar mass was found to be a poststenotic dilatation due to a severe pulmonary valve stenosis. Percutaneous balloon valvuloplasty of the pulmonary valve was successfully done, and the patient is well 2 years after the procedure.

Topical treatment of life threatening haemoptysis from aspergillomas.

BACKGROUND: The efficacy of topical treatment of 12 episodes of severe life threatening haemoptysis from a pulmonary aspergilloma in 11 patients is reviewed. METHODS: A retrospective review was performed on five white and six African-American patients of mean age 49 years. The underlying diseases were bronchiectasis, sarcoidosis, tuberculosis, or histoplasmosis. The patients were prospectively considered poor surgical risks because they had a forced expiratory volume in one second (FEV1) of < 50% predicted and an arterial oxygen tension (PaO2) of < 7.95 kPa breathing room air. As surgical intervention was not possible, local intracavitary instillation of sodium or potassium iodide was performed. Two patients were previously treated with amphotericin B. In one patient sodium iodide alone was used and in the remaining eight potassium iodide alone was instilled. The transcricothyroid approach was used in six patients and the percutaneous approach in five. RESULTS: Haemoptysis ceased within 72 hours in all patients after the instillation of sodium or potassium iodide. There was no morbidity or mortality, and side effects included slight irritation on instillation of the iodide solution and occasional cough which was easily controlled. All patients were alive at least one year later. CONCLUSION: Intracavitary treatment is a viable option in the poor risk patient with life threatening haemoptysis from an aspergilloma.

The etiology of pulmonary edema in fresh water near-drowning.

Drowning is a significant cause of death in children and young adults. It is thought to result from the inhalation of either fresh or sea water resulting in lung damage and ventilation-perfusion mismatching. The clinical course, chest roentgenographs, serum electrolytes, alveolar-arterial oxygen gradient, and complete blood count of 10 fresh water drowning victims with pulmonary edema were recorded. Six responded dramatically clinically and radiographically within 24 hours, and most did not have significant alterations of their serum electrolyte levels, especially serum chloride. On the basis of the rapid clearing of the pulmonary edema and the lack of evidence of significant fluid aspiration, neurogenic pulmonary edema is postulated to have played a role in the development of the pulmonary edema in these patients.

Educational and long-term therapeutic intervention in the ED: effect on outcomes in adult indigent minority asthmatics.

Minorities have increased morbidity and mortality rates resulting from asthma. The segment of minorities that is socioeconomically depressed often uses the emergency department (ED) as their primary site of medical care. For these reasons, we provided major long-term therapeutic intervention as well as intensive education in the ED for indigent adult African American asthmatics. We intervened in the cases of 30 patients who were frequent visitors to the ED over the previous 2 years. The intervention consisted of 1 hour of education in the ED before discharge regarding the prevention of asthma, the importance of decreasing inflammation as a means of improving asthma control, self-monitoring with a peak flow meter, and a demonstration of correct inhalation technique with metered-dose inhalers and a spacer device. Further, the intervention included management consistent with recent NIH Guidelines, stressing inhaled corticosteroids. After the intervention in the ED, patients were scheduled for follow-up asthma clinic visits. Outcome measures were ED visits and hospitalizations for 1 year after the ED intervention. Using the same inclusion/exclusion criteria, a retrospective control group of 22 patients for the same time period was compared with the intervention group. Before our intervention, the mean number of ED visits per patient for the previous 2 years was 4.4 +/- 2.7, and after the intervention, 2.6 +/- 2.6 (P < .01). The control group did not show a difference in the number of ED visits (3.4 +/- 2.6 before and 3.5 +/- 2.7 after, P = .96). After the intervention, the mean number of hospitalizations decreased significantly in the study group (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Significant reduction in methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia associated with the institution of a prevention protocol.

OBJECTIVE: To determine whether the institution of a methicillin-resistant Staphylococcus aureus prevention protocol was associated with a decrease in methicillin-resistant S. aureus ventilator-associated pneumonia in long-term, acute care ventilator patients. DESIGN: A retrospective chart review comparing the number of episodes of clinical pneumonia per patient ventilator day in the 12 months preceding and 24 months following the introduction of the protocol. SETTING: University affiliated, long-term, acute care ventilator hospital. PATIENTS: Long-term, acute care ventilated patients who presented with clinical pneumonia. INTERVENTIONS: Addition of a methicillin-resistant S. aureus prevention protocol. In addition to universal precautions, the protocol consisted of mupirocin 2% ointment applied to the anterior nares, and whole body washing with chlorhexidine. All patients were given mupirocin and chlorhexidine twice weekly. Patients were cohorted in the same room if they were, or had been, infected or colonized with methicillin-resistant S. aureus in any anatomical location or at any time. This procedure replaced strict isolation of methicillin-resistant S. aureus-infected or colonized individuals. MEASUREMENTS AND MAIN RESULTS: Clinical pneumonia was diagnosed when a patient developed fever, bronchorrhea, increased white blood cell count, methicillin-resistant S. aureus isolated from the tracheal aspirate, and new or increasing infiltrate on chest roentgenograph. During the 12 months preceding the protocol, there were 0.2% episodes of methicillin-resistant S. aureus ventilator-associated pneumonia per ventilated patient day compared with 0.026% in the 24 months after the protocol (p < .001). The relative and absolute risk reductions associated with the introduction of the protocol were 87% and 6, respectively. CONCLUSIONS: The period following the institution of the protocol showed a significant reduction in episodes of clinical pneumonia compared with the 12-month period preceding the use of the protocol (p < .001). Thus, we conclude that the introduction of this protocol is associated with a significant decrease in methicillin-resistant S. aureus ventilator-associated pneumonia.

Tracheal aspirate correlates with protected specimen brush in long-term ventilated patients who have clinical pneumonia.

STUDY OBJECTIVE: This study was undertaken to determine whether tracheal aspirate cultures correlate with protected specimen brush (PSB) cultures in the diagnosis of probable ventilator-associated pneumonia (VAP). DESIGN: Retrospective evaluation of 52 episodes of clinical pneumonia in 38 patients who underwent bronchoscopy and PSB as well as tracheal aspirate cultures. SETTING: The study took place in long-term, acute care hospital associated with a university medical school. This hospital specializes in ventilator-assisted patients. PATIENTS: The patient population consisted of long-term ventilated patients (average ventilation time was 22 weeks; range, 4 weeks to 3 years) who presented with the clinical diagnosis of VAP (fever, increased white blood cell count, new infiltrate on chest radiograph, and bronchorrhea). No patient had received antibiotics for the preceding 5 days at the time of bronchoscopy or tracheal aspirate culture. MEASUREMENTS: The tracheal aspirate and PSB culture and sensitivities results. RESULTS: Identical organisms were recovered in both the tracheal aspirate and PSB cultures in 36 of 52 episodes of VAP (69 percent). No organism was recovered in either the tracheal aspirate or the PSB in 4 of 52 suspected episodes (8 percent). Positive bacterial cultures in the tracheal aspirate but not the PSB were found in 8 of 52 (15 percent) episodes. In 3 of 52 episodes (6 percent), 1 isolate of pathogenic bacteria was found on PSB and 2 were found on tracheal aspirate cultures. However, all three isolates had the similar antibiotic sensitivities. In the final episode, the PSB culture grew an organism that was not present in the tracheal aspirate culture (2 percent). When comparing the tracheal aspirate with the PSB, the following were calculated: sensitivity = 97.7 percent; specificity = 50 percent; positive predictive value = 91.3 percent; and negative predictive value = 80 percent. CONCLUSION: Tracheal aspirate cultures correlate with PSB cultures in patients receiving long-term ventilation who have clinical pneumonia, and they can be used to direct initial antibiotic therapy in this group of patients.

Case report: acute postoperative respiratory failure caused by Chlamydia pneumoniae and diagnosed by bronchoalveolar lavage.

Most Chlamydia pneumoniae infections are mild, but 10% develop into pneumonia. C. pneumoniae has been observed in hospital in intubated patients undergoing major surgery or admitted with severe trauma. A patient with squamous cell carcinoma in whom severe pneumonia developed postpneumonectomy and who required mechanical ventilation is presented. The patient was initially treated for nosocomial bacterial pneumonia with the broad spectrum antibiotics ceftazidime, amikacin, and vancomycin. The patient underwent a bronchoalveolar lavage, from which C. pneumoniae was grown. Generally, these patients are a high-risk mortality group. Only after substituting the above antibiotics with doxycycline, to which C. pneumoniae was sensitive, did the pneumonia respond. Whether this was a nosocomial or a community-acquired pneumonia is uncertain.

Perception of anxiety as a contributing factor of asthma: indigent versus nonindigent.

Although asthma is not an emotional or psychological disease, strong emotions can sometimes make asthma worse. Asthmatic attacks and reductions in FEV1 have been intentionally induced in asthmatic patients through exposure to emotional stimuli. People of lower socioeconomic status have been associated with higher prevalences of both anxiety and depression. Therefore, a group of indigent (IP) and nonindigent privately insured asthmatic patients (non-IP) were surveyed to determine their perceptions of asthma triggers. The patients responded to several possible triggers by the following descriptors: never, rarely, sometimes, frequently, always. There were no significant differences at the 0.05 level between the groups in age, gender, or length of history of asthma. In response to the question pertaining to asthma triggered when upset or anxious, 51% of 57 patients responded to the "frequently" or "always" category in the IP compared to 19% of 52 in the non-IP. Further research is warranted to explain these differences. If these differences are real, optimal therapies for psychogenic asthma (e.g., addition of anticholinergic aerosols) or the treatment of anxiety itself in the IP need to be evaluated.