Multisystem organ failure predicts mortality of ICU patients with acute respiratory failure secondary to AIDS-related PCP.

OBJECTIVE: To evaluate the ability of a variety of scoring systems to predict mortality of patients admitted to an intensive care unit (ICU) with acute respiratory failure (ARF) secondary to AIDS-related Pneumocystis carinii pneumonia (PCP). METHODS: All patients with AIDS-related PCP admitted to ICU at St. Paul's Hospital between January 1, 1985 and April 1, 1991 were reviewed. For each case, the following scores were calculated from data obtained within 24 h of ICU admission: acute physiology and chronic health evaluation II (APACHE II); acute lung injury score; AIDS score as described by Justice and Feinstein; and modified multisystem organ failure (MSOF) score. The serum lactate dehydrogenase (LDH) level was also recorded when obtained within 24 h of ICU admission. RESULTS: A total of 52 ICU admissions in 51 patients were studied. Overall mortality was 65 percent. Mortality increased with increasing MSOF (p < 0.05) score and LDH (p < 0.05). Based on receiver operating characteristic (ROC) curves, the MSOF score and the LDH were found to be good predictors of mortality. Multivariate logistic regression showed that the MSOF score was the only independent predictor of mortality (p < 0.05). The AIDS score, APACHE II, and the acute lung injury score were not significantly associated with mortality. Addition of the serum LDH level improved the performance of both the MSOF and AIDS scores, though the AIDS score plus LDH performed no better than the LDH alone. Of all the scores tested, the MSOF plus LDH level was the best (p < 0.005) predictor of mortality. CONCLUSIONS: The modified MSOF score and the serum LDH level are the best predictors of mortality of patients admitted to ICU with ARF secondary to AIDS-related PCP. The performance of the MSOF score was enhanced when the LDH level was added. The AIDS score, APACHE II, and the acute lung injury score were not found to be useful in this group of critically ill patients.

Decreasing frequency but worsening mortality of acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVE: To describe changes in incidence and outcome of acute respiratory failure (ARF) due to AIDS-related Pneumocystis carinii pneumonia (PCP) at a tertiary care center over the 4-year period starting April 1, 1987 with reference to previously reported data from the preceding 6 years. METHODS: All patients admitted to St. Paul's hospital with a diagnosis of AIDS-related PCP during the study period were reviewed with regard to diagnostic, clinical, therapeutic, and outcome variables. RESULTS: A total of 456 episodes of PCP were diagnosed during the study period. These were compared against 127 cases diagnosed between 1981 and 1987. The frequency of hospitalization for PCP decreased to 78% in 1987 to 1991 from 100% in 1981 to 1987 (p < or = 0.001). A similar decreasing trend was observed with regard to the incidence of PCP-related ARF that declined from 21% in 1981 to 1987 to 9% in 1987 to 1991 (p = 0.009). Despite this, overall PCP-related mortality remained stable at 12% in 1981 to 1987 and 9% in 1987 to 1991 (p = 0.26). The proportion of patients with PCP-related ARF who received mechanical ventilation decreased from 89% in 1981 to 1987 to 64% in 1987 to 1991 (p < 0.001). Despite this, the case fatality rate among mechanically ventilated patients increased from 50% in 1981 to 1987 to 89% in 1987 to 1991 (p = 0.003). These changes were associated with a significant change in the pattern of use of corticosteroids as adjunctive therapy for AIDS-related PCP. In 1985 to 1986, nearly 100% of patients admitted to the ICU received corticosteroids only after admission to the ICU, following the development of ARF. In contrast, in 1989 to 1990, 50% of patients were admitted to the ICU already receiving systemic corticosteroids. The rise in the proportion of patients receiving corticosteroids prior to ICU admission between these two intervals was statistically significant (p = 0.017). CONCLUSION: Our data show a decreasing frequency but a worsening mortality of ARF secondary to AIDS-related PCP. We conclude that ARF secondary to AIDS-related PCP developing despite maximal therapy, including adjunctive corticosteroids, carries a dismal prognosis.

Surgical management of pneumothorax in patients with acquired immunodeficiency syndrome.

Pneumocystis carinii pneumonia in a patient with acquired immunodeficiency syndrome may cause severe alveolar damage, resulting in pneumothoraces that are often bilateral, recurrent, and refractory to accepted methods of treatment. The clinical features, management, and follow-up results were assessed in 22 consecutive patients who presented with a pneumothorax and acquired immunodeficiency syndrome. Seventeen patients died within the time frame of this study. Their average survival time was 147 days. Five surviving patients have lived an average of 366 days. We proposed an algorithm to assist in the management of pneumothoraces in these patients. We concluded that pneumothorax in patients with acquired immunodeficiency syndrome is prognostic of short-term survival. The results in the treatment of pneumothorax in the patient with acquired immunodeficiency syndrome are related to the pathologic lesions of the lung that are associated with Pneumocystis pneumonia and not to the surgical treatment that is employed.

An infected mediastinal cyst.

The authors describe a 43-year-old patient who had a mediastinal mass that became infected after a transbronchial needle aspirate biopsy. A paraspinal, extrapleural window with a saline-lidocaine mixture was created that allowed the placement of a percutaneous drainage catheter into the infected lesion. This procedure resulted in an excellent clinical outcome, and obviated the need for a thoracotomy and more invasive surgical management.

Patterns of response to inhaled bronchodilators in asthmatics.

In response to inhaled bronchodilators, asthmatic subjects may show a predominant increase in expiratory flow rate (flow responders) or forced vital capacity (volume responders). The pattern of response could relate to the site of expiratory flow limitation and/or the site of action of the inhaled bronchodilator. We studied 15 asthmatic subjects, and measured lung volumes and maximal expiratory flow-volume curves while they breathed room air and 80% He-20% O2 (He-O2) before and after inhalation of fenoterol 400 micrograms (Berotec), and ipratropium bromide 40 micrograms (SCH 1000). Subjects were categorized as flow responders (FR) or as volume responders (VR) by the ratio delta FEV1/delta FVC (ratio less than 1 predominant VR, ratio greater than 1 = predominant FR). The site of expiratory air-flow limitation was assessed by the percent increase in maximal expiratory flow breathing He-O2 at an absolute lung volume (delta Vmax), and the change in He response from control was calculated (delta delta Vmax). The ratio delta FEV1/delta FVC varied between 0 and 10 and did not correlate with initial density dependence. There was no difference in the pattern or apparent site of response to Berotec or SCH 1000. There was a positive relationship between control FEV1 and FVC percent predicted and delta FEV1/delta FVC. The subjects with worse pulmonary function showed a decrease in He-O2 response postbronchodilator and a predominant volume response suggesting recruitment of peripheral diseased airways.

The detection of small airways disease.

In order to investigate the relationship between pulmonary function and disease of the membranous and respiratory bronchioles, we studied 96 patients who required lobectomy for removal of a solitary pulmonary nodule. A subgroup of patients with forced expiratory volume in one second (FEV1) greater than 80% predicted were further analyzed to determine if abnormalities in tests designed to detect peripheral airways disease actually correlated with the pathology found in these airways. Analysis of the data shows that inflammation in both respiratory and membranous bronchioles, goblet cell metaplasia of the epithelium in membranous bronchioles, and decreasing muscle in the respiratory bronchioles are the pathologic features that are associated with deterioration of the FEV1. When the FEV1 is greater than 80% of the predicted value, inflammation of the respiratory bronchioles and fibrosis of both membranous and respiratory bronchioles increase with decreasing FEV1. Tests of specialized pulmonary function appear to correlate with epithelial pathologic parameters of membraneous bronchioles and inflammation and fibrosis of respiratory bronchioles. When patients with FEV1 greater than 80% predicted were subdivided according to the number of abnormal tests of small airways function, there was a significant increase in inflammation of the walls of respiratory bronchioles when 2 tests were abnormal and increases in both airway wall and intralumenal inflammatory cells as well as increased wall fibrosis when 3 tests were abnormal. We conclude that when the FEV1 is greater than 80% predicted, abnormalities in the tests for small airway disease reflect pathologic changes in the respiratory bronchioles.

Morphology of peripheral airways in current smokers and ex-smokers.

To investigate the effect of smoking status on pulmonary function and pathologic changes in the peripheral airways, we studied 97 patients who underwent thoracotomy for coin lesions. The patients were divided into 4 groups: nonsmokers (n = 9), current smokers (n = 51), and those who had ceased smoking for less than (n = 18) or more than (n = 19) 2 yr prior to surgery. We found that current smokers had evidence of air-flow obstruction with abnormal lung volumes when compared with nonsmokers. Ex-smokers had lung volumes similar to those of nonsmokers, but showed evidence of obstruction, with the FEV1/FVC between the values found for nonsmokers and current smokers. Examination of the small airways showed that the membranous bronchioles of current smokers and ex-smokers displayed only increased goblet cell metaplasia when compared with those in nonsmokers; the respiratory bronchioles of current and ex-smokers showed increases in intraluminal and airway wall inflammatory cells, wall fibrosis, and pigment deposition. We conclude that patients who currently smoke cigarettes have reduced lung function that is associated with abnormalities of airway structure. Although those who have stopped smoking have function that is closer to the nonsmoking group, there is no apparent difference in structural change between current and ex-smokers.

Corticosteroids prevent early deterioration in patients with moderately severe Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS)

OBJECTIVE: To determine whether oral corticosteroids can prevent early deterioration in patients with acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia. DESIGN: Prospective, double-blind, placebo-controlled, randomized trial. METHODS: Included patients were having their first P. carinii pneumonia episode, had no other known active pulmonary pathology, had no contraindications for corticosteroids, received no anti-P. carinii pneumonia medications for more than 48 hours, and had oxygen saturation by pulse oximetry of 85% or more and less than 90% at rest or a 5-percentage-point decrease in oxygen saturation with exercise while breathing room air. Consenting subjects were randomly assigned to prednisone, 60 mg/d for 7 days, followed by a progressive tapering over 14 days or to an identical placebo. Early deterioration, the endpoint of the trial, was defined as a 10% decrease in baseline oxygen saturation on day 3 or thereafter. The cases of patients developing early deterioration were considered to be failures of treatment; the code was then broken, and the patient's treatment was left to the judgment of the treating physician. Sequential analysis was done with the primary variable being development of early deterioration. RESULTS: The trial was terminated 5 April 1989 on the basis of the sequential analysis when a total of nine episodes of early deterioration had occurred in the first 37 patients at an overall significance level of P = 0.0136. A total of 8 of 19 placebo-treated patients (42.1%) developed early deterioration compared with only 1 of 18 patients (5.6%) treated with corticosteroids. Baseline characteristics were not statistically different between the two treatment groups. The adjusted odds ratio for the treatment effect was 5.87 (95% CI, 1.27 to 27.4). The adjusted point estimates for the probability of early deterioration in the placebo and corticosteroid groups were 43% and 12%, respectively. All 8 patients in the placebo group developing early deterioration recovered rapidly with addition of corticosteroid treatment. The single patient with early deterioration in the corticosteroid group died on day 6 from overwhelming P. carinii pneumonia, as documented at autopsy. The corticosteroid group had an increased exercise tolerance on day 7 that persisted at day 30. CONCLUSION: Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with moderately severe AIDS-related P. carinii pneumonia.

Unexpected lung lesions in high resolution computed tomography (HRTC) among patients with advanced HIV disease.

The present pilot study was undertaken to characterize the frequency of lung lesions in asymptomatic human deficiency virus (HIV) infected individuals with advanced HIV disease. Thirty two consecutive HIV+ homosexual males assessed for initiation of Pneumocystis carinii pneumonia (PCP) prophylaxis, were prospectively studied. All patients underwent a complete medical history, physical examination, pulmonary function tests and high resolution computed tomography (HRCT). HRCT scans were read by a single radiologist, who was blind as to the clinical status of the patient. Unexpected HRCT scan lesions were found in 60% of patients. There were no statistically significant differences between patients with normal and abnormal HRCT with respect to age, height, weight, CD4+ count, smoking history, serum albumin, alpha 1-antitrypsin level or body mass index. Forced vital capacity (FVC) (% of predicted) and peak expiratory flow rate (PEFR) (% pred) were not significantly different between groups. For patients with normal and abnormal HRCT forced expiratory volume in one second (FEV1) (% pred) was 99 +/- 12 vs 92 +/- 16, FEV1/FVC was 82 +/- 5 vs 76 +/- 9, and forced mid-expiratory flow (FEF25-75) (% pred) was 100 +/- 24 vs 77 +/- 27, respectively. There were no statistically significant differences between patients presenting with destructive versus nondestructive lung HRCT lesions. Our results demonstrate that as many as 60% of HIV-infected patients have unexpected abnormalities on HRCT at the time of starting PCP prophylaxis. We speculate that these lesions may contribute to the high frequency of spontaneous pneumothoraces previously reported in this patient population.

Exponential analysis of the lung pressure-volume curve as a predictor of pulmonary emphysema.

To compare the predictive value of different pulmonary function tests in the diagnosis of morphologic emphysema, we performed measurements of subdivisions of lung volume, gas exchange, maximal expiratory flow rates, and static deflation pressure-volume curves on 55 subjects prior to surgery for removal of an isolated peripheral pulmonary lesion. Emphysema was graded on the resected lung specimen and the pressure-volume data were fitted to an exponential equation (V = A - Be-KP). By chi-square analysis, K was the best predictor of emphysema in individual subjects and it was the only test that distinguished subjects with moderate emphysema from subjects with mild or without emphysema, but K did not distinguish those with mild emphysema from those without emphysema. As a group those with mild emphysema were distinguishable from predicted normal with K and elastic recoil pressures at 90 and 60% of predicted total lung capacity. We conclude that minimal emphysema may be detected by exponential analysis of the lung pressure-volume curve.

Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. A randomized, placebo-controlled study.

OBJECTIVE: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). PARTICIPANTS: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. INTERVENTION: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of 5 doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. RESULTS: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and 5 occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P less than 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. CONCLUSION: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia.