Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation.

BACKGROUND: At many lung transplant centers, right heart catheterization and transthoracic echocardiogram are part of the routine pre-transplant evaluation to measure pulmonary pressures. Because decisions regarding single vs bilateral lung transplant procedures and the need for cardiopulmonary bypass are often made based on pulmonary artery systolic pressures, we sought to examine the relationship between estimated and measured pulmonary artery systolic pressures using echocardiogram and catheterization, respectively. METHODS: We retrospectively reviewed all patients in our program who had measured pulmonary hypertension (n = 57). Patients with both echocardiogram-estimated and catheterization-measured pulmonary artery systolic pressures performed within 2 weeks of each other were included (n = 19). We analyzed results for correlation and linear regression in the entire group and in the patients with primary pulmonary hypertension (n = 8) and pulmonary fibrosis (n = 8). RESULTS: In patients with primary pulmonary hypertension, pulmonary artery systolic pressure was 94 +/- 27 and 95 +/- 15 mm Hg by echocardiogram and catheterization, respectively, with r(2) = 0.11; in patients with pulmonary fibrosis, 57 +/- 23 and 58 +/- 12 mm Hg with r(2) = 0.22; and in the whole group, 76 +/- 29 and 75 +/- 23 mm Hg with r(2) = 0.50. Thirty-two additional patients had mean pulmonary artery systolic pressure = 48 +/- 16 mm Hg by catheterization but either had no evidence of tricuspid regurgitation by echocardiogram (n = 22) or the pulmonary artery systolic pressure could not be measured (n = 10). CONCLUSIONS: In patients with pulmonary hypertension awaiting transplant, pulmonary artery systolic pressures estimated by echocardiogram correspond but do not serve as an accurate predictive model of pulmonary artery systolic pressures measured by catheterization. Technical limitations of the echocardiogram in this patient population often preclude estimating pulmonary artery systolic pressure.

Effects of fiberoptic bronchoscopy during mechanical ventilation in a lung model.

STUDY OBJECTIVES: To evaluate the effects of fiberoptic bronchoscopy (FOB) on delivered volumes and pressures during mechanical ventilation, utilizing a lung model. DESIGN: Bench study. SETTING: Laboratory. MATERIALS AND METHODS: Using varying-sized endotracheal tubes (ETTs), we ventilated a lung model at two levels of compliance utilizing different modes and parameters of ventilation. After establishing baseline measurements, the bronchoscope was inserted and measurements repeated. MEASUREMENTS AND RESULTS: During controlled mechanical ventilation (CMV) with a preset high-pressure limit (HPL), tidal volumes (VTs) were reduced from 700 mL to 0 to 500 mL following insertion of the bronchoscope. Increasing the HPL to 120 cm H(2)O resulted in a VT of 40 to 680 mL. Changing from square to decelerating flow waveform resulted in no consistent difference in VT. Auto-positive end-expiratory pressure (auto-PEEP) of 0 to 41 cm H(2)O was present under most conditions. Higher rates and lower peak inspiratory flows were associated with higher levels of auto-PEEP. In the pressure-control (PC) mode, using a preset inspiratory pressure level (IP), VT was reduced from 700 mL to 40 to 280 mL following insertion of the bronchoscope. Maximum IP (100 cm H(2)O) increased VT to 260 to 700 mL. Auto-PEEP was less in the PC mode. CONCLUSIONS: Extreme care must be taken when bronchoscopy is performed on a patient receiving mechanical ventilation. Extremely low VT and significant auto-PEEP may develop unless flow, respiratory rate, mode, and ETT size are carefully selected. The PC mode delivered more volume than did the CMV mode. When performing FOB during mechanical ventilation, the inside diameter of the ETT should be > or = 2.0-mm larger than the outside diameter of the bronchoscope to maintain volume delivery and minimize the development of auto-PEEP.

A randomized, placebo-controlled study to evaluate the role of salmeterol in the in-hospital management of asthma.

STUDY OBJECTIVES: To assess the safety and efficacy of salmeterol xinafoate as an adjunct to conventional therapy for the in-hospital management of acute asthma. DESIGN: A prospective, double-blind, randomized placebo-controlled trial. SETTING: Medical wards of a large university-based hospital. PATIENTS: Forty-three patients admitted for an acute exacerbation of asthma. INTERVENTIONS: Salmeterol (42 microg) or two puffs of placebo every 12 h in addition to standard therapy (short-acting beta-agonists, corticosteroids, and anticholinergic agents). RESULTS: No clinically adverse effects were seen with the addition of salmeterol to conventional therapy. After salmeterol, there was no difference in pulse, respiratory rate, oxygen saturation by pulse oximetry, severity of symptoms, or dyspnea score. Patients receiving salmeterol had greater FEV(1) percent improvements than the placebo group at 12, 24, 36, and 48 h. These findings were not statistically significant. By paired Student's t tests, there were significant improvements in FEV(1) (p = 0.03) and FVC (p = 0.03) in the salmeterol group after 48 h of treatment with no comparable improvement in the placebo group. In a subgroup analysis of patients with an initial FEV(1) < or = 1.5 L, the absolute FEV(1) percent improvement for salmeterol vs placebo was 51% vs 16% at 24 h and 54% vs 40% at 48 h. The relative FEV(1) percent improvement for salmeterol vs placebo was 17% vs 8% at 24 h and 18% vs 14% at 48 h. CONCLUSION: The addition of salmeterol to conventional therapy is safe and may benefit hospitalized patients with asthma. Further studies are needed to clarify its role in the treatment of acute exacerbation of asthma.

A low incidence of posttransplant lymphoproliferative disorder in 109 lung transplant recipients.

STUDY OBJECTIVES: The incidence of posttransplant lymphoproliferative disorder (PTLD) has been reported to range from 6.4 to 20% in lung transplant (LT) recipients. Postulated contributing factors include Epstein-Barr virus (EBV) infection and the use of immunosuppression, particularly muromonab-CD3 (OKT3)(Orthoclone OKT-3; Ortho Biotech; Raritan, NJ). We sought to examine these PTLD risk factors in 109 LT recipients at our institution who survived > 1 month. DESIGN: Retrospective review of EBV serology of all LT recipients at our institution. Our standard transplant protocol includes OKT3 for induction and refractory rejection, as well as lifelong acyclovir for herpes prophylaxis. We do not perform EBV donor-recipient matching. SETTING: A university-based LT center. RESULTS: We found that 5 of 109 patients were serologically negative for EBV prior to lung transplantation, and all of these patients converted following lung transplantation. The mean time to conversion was 151 days (range, 11 to 365 days). One fatal case of PTLD was documented in an EBV seroconverter (one of five patients) 12 weeks status posttransplantation for lymphangioleiomyomatosis. One nonfatal extrathoracic PTLD was documented in a seropositive patient (1 of 104 patients) 33 months posttransplantation. CONCLUSIONS: We conclude the following: (1) PTLD in LT recipients may have a lower incidence (2 of 109 patients; 1.8%) than previously reported, despite an aggressive immunosuppressive regimen; and (2) the incidence of PTLD is higher in patients with primary EBV infection (20% vs 1%).

Use of balloon-expandable metallic stents in the management of bronchial stenosis and bronchomalacia after lung transplantation.

STUDY OBJECTIVES: Bronchial stenosis (BS) and bronchomalacia (BM) are often associated with lung allograft rejection or infection in lung transplant (LT) recipients. We reviewed our experience using balloon-expandable metallic (Palmaz) stents in the management of BS and BM in LT. DESIGN: Retrospective review of cases. PATIENTS: LT recipients with bronchoscopic and spirometric evidence of BS and BM. INTERVENTIONS: Serial balloon dilation was performed for BS. Stent placement was done for refractory or recurrent BS, or persistent focal BM. RESULTS: Twelve of 129 LT bronchial anastomoses at risk (9.3%) had complications, which included 11 BS and 5 BM. Four BS were accompanied by BM either concurrently or subsequently. The only isolated BM was associated with acute rejection and resolved after appropriate medical therapy. Balloon dilations alone were successful in relieving BS in three cases. Seven patients received a total of 11 stents. Stents were placed under conscious sedation using a flexible bronchoscope. Five of the seven patients had spirometric improvements after stent placements. One patient had no spirometric improvement, and another died before a follow-up study was done. There were no complications during stent placements. However, complications after stent placements included partial dehiscence of the stent from the bronchial wall, stent migration, partial obstruction of a segmental bronchial orifice by a stent in the main bronchus, and longitudinal stent collapse. One stent was successfully removed using a flexible bronchoscope in the endoscopy suite, and two others were removed by rigid bronchoscopy in the operating room. CONCLUSIONS: Endobronchial placement of the Palmaz stent in LT recipients is relatively easy, and it can be removed if needed. However, because there are significant potential complications, the future use of this stent as an airway prosthesis in LT remains unclear.

Effects of continuous bed rotation and prolonged mechanical ventilation on healthy, adult baboons.

OBJECTIVE: To study, in a model of prolonged mechanical ventilation, the role of continuous bed rotation on lung function and pathology. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Healthy adult baboons (Papio cynocephalus), anesthetized with ketamine, sedated, paralyzed, mechanically ventilated for 11 days, and monitored with pulmonary and peripheral arterial catheters. INTERVENTIONS: Animals were divided into two experimental groups: a) mechanical ventilation alone (control, n = 7); and b) mechanical ventilation with continuous bed rotation therapy to 45 degrees (continuous rotation group, n = 5). Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 12 mL/ kg. Bronchoalveolar lavage was performed through a fiberoptic bronchoscope. Nursing care procedures, antacids, enteral feeding, and prophylactic antibiotics were administered. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, pulmonary functions, lung volumes, arterial blood gases, and chest radiographs were done daily. Bronchoalveolar lavage was performed at days 0, 7, and 11. There were no significant changes in hemodynamics, gas exchange, or pulmonary functions during the study period in either group. Microbiological surveillance cultures were negative in both experimental groups. In the control group after 7 days, six of seven animals developed patchy atelectasis; by day 11, two of seven animals demonstrated persistent radiologic abnormalities. Bronchoalveolar lavage neutrophils were significantly increased in control animals at days 7 and 11. Lung pathology in the control group showed areas of bronchiolitis, with surrounding bronchopneumonia in five of seven animals. None of the continuous rotation animals showed any radiologic or morphologic abnormalities. CONCLUSIONS: Prolonged mechanical ventilation in the control group resulted in atelectasis, increased concentrations of bronchoalveolar lavage neutrophils, and mild pneumonitis. These effects were not associated with changes in lung volumes, oxygenation, or hemodynamic parameters. Continuous bed rotation helped to prevent these abnormalities.

Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons.

OBJECTIVE: To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated. Animals were monitored with pulmonary arterial and peripheral arterial catheters. INTERVENTIONS: Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 15 mL/kg. Pulmonary function tests, including lung volumes, arterial blood gases, and chest radiographs were also monitored. Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction. Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered. In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation. On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed. After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation. Diaphragmatic strength and endurance were measured on days 0 and 11. Diaphragmatic endurance was determined by an inspiratory resistive loading protocol. There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation. On day 7, the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in all but two of the animals. Lung pathology showed mild, focal pneumonitis. By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36%. CONCLUSIONS: Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function. However, significant impairment in diaphragmatic endurance and strength were seen. Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease.

Acute lupus pneumonitis with normal chest radiograph.

Patients with acute lupus pneumonitis (ALP) usually have hypoxemia, patchy infiltrates evidenced on a chest x-ray film, and an incomplete response to corticosteroids with high mortality. In contrast, lupus patients with a syndrome of acute reversible hypoxemia (SARH) have hypoxemia with normal chest x-ray films and a rapid response to corticosteroids. We present a case of biopsy-proven ALP with normal initial chest x-ray films, and a normal CT scan. We hypothesize that a continuum of vascular and parenchymal abnormalities may exist in the lungs of lupus patients. This case also illustrates the insensitivity of routine chest radiographs in demonstrating mild or early pneumonitis.

Emergency treatment of asthma.

Rapid and directed evaluation of the acutely ill patient with asthma allows for the assessment of severity of obstruction. Aggressive therapy with inhaled beta-agonists, corticosteroids, and supplemental oxygen remains the cornerstone of therapy for patients presenting to the hospital. Patients demonstrating an incomplete response to inhaled beta-agonists will require inhaled anticholinergics and may benefit from subcutaneous epinephrine or terbutaline. Theophylline should be continued in all patients who are chronically maintained on this medication and may benefit patients admitted to the hospital for a serious exacerbation. Deterioration or failure to improve despite optimal treatment identifies those patients who are likely to require mechanical ventilation and who should be closely observed in the intensive care unit.

Development of intracranial tuberculomas while receiving therapy for pulmonary tuberculosis [corrected].

Development of tuberculomas on adequate tuberculosis therapy is an uncommon event. This case report describes a patient who developed multiple intracranial tuberculomas while receiving adequate supervised outpatient therapy for sensitive pulmonary tuberculosis who was documented to have no intracranial lesions prior to initiation of treatment.

Medium term functional results of single-lung transplantation for endstage obstructive lung disease.

Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV1 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV1/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to the new lung graft. After SLT, patients have reduced maximum oxygen consumption (VO2max 40 to 60% predicted) but do not have ventilatory limitation to exercise and can carry out daily activities without compromise. We conclude that SLT is a viable medium-term therapeutic option for endstage obstructive lung disease. The long-term future of this technique remains to be determined.

Single lung transplantation in patients with systemic disease.

OBJECTIVE: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival. RESULTS: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.

Pathophysiology of acute respiratory failure.

The term respiratory failure implies the inability to maintain either the normal delivery of oxygen to tissues or the normal removal of carbon dioxide from the tissues. There are actually three processes involved: the transfer of oxygen across the alveolus, the transport of tissues (by cardiac output), and the removal of carbon dioxide from the blood into the alveolus with subsequent exhalation into the environment. Failure of any step in this process can lead to respiratory failure. An overview of the normal physiology of pulmonary gas exchange and the pathophysiology of respiratory failure is presented in this article.

Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons.

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.

O2- and pneumonia-induced lung injury. I. Pathological and morphometric studies.

The physiological, morphological, and morphometric findings of several lung injury models in baboons have been compared in the following six study groups: 1) initial injury with oleic acid followed by ventilation with 100% O2, 2) ventilation with 100% O2, 3) ventilation with 80% O2, 4) ventilation with 80% O2 followed by inoculation of Pseudomonas aeruginosa, 5) ventilation with 40% O2, and 6) normal nonventilated room-air-breathing animals. The animals were maintained for 11 days in an intensive care unit. Light microscopically, animals ventilated with 40 and 80% O2 showed mild lung injury, consisting mostly of an increase in alveolar macrophages in peribronchiolar sites and focal alveolar wall widening. The 100% O2-oleic acid, 100% O2, and 80% O2-Pseudomonas-treated baboons showed mixed exudative-reparative diffuse alveolar lesions. Ultrastructurally, the type II cells of these three groups had significantly altered morphology with aberrations of lamellar body configurations. Morphometric findings showed increases in type II and interstitial cells and decreases in type I and endothelial cells in these injured animals. A striking finding was that the physiological, morphological, and morphometric changes of an 80% O2-Pseudomonas insult was as injurious as 100% O2. This synergistic effect of hyperoxia and infection very likely reflects the most frequent evolution of adult respiratory distress syndrome in patients in intensive care units.

O2- and pneumonia-induced lung injury. II. Properties of pulmonary surfactant.

Pulmonary surfactant was isolated from the lavage fluids of animals during the course of exposure to 100% O2, 80% O2, 40% O2, or 80% O2 plus 10(8) Pseudomonas aeruginosa instilled intratracheally and analyzed for its phospholipid composition. After 4-5 days of exposure to 100% O2, disaturated phophatidylcholine (DSPC) decreased to 87% of control, whereas the ratio of phosphatidylglycerol to phosphatidylinositol (PG/PI) was 37% of control. Longer periods of ventilation with 100% O2 resulted in DSPC falling to less than 40% of control. The injury was not reversed by reducing the O2 to 50%; rather, a progressive deterioration ensued. Acute respiratory failure (ARF) induced by 5 days of bacterial infection was very similar to that seen after 5 days of exposure to 100% O2. Ventilation with 80% O2 for 6 days resulted in smaller changes in DSPC but with differences in PG/PI comparable to those seen with 100% O2 or infection. We conclude that the ability of the type II cell to synthesize surfactant of normal composition is significantly impaired in these models of ARF. The earliest index of biochemical modification is the substantial change in PG/PI, which may be predictive of early lung injury. Further exacerbation of the injury could result in the reduction of DSPC content, with subsequent changes in lung mechanics and gas exchange.

von Hippel-Lindau syndrome presenting as pancreatic endocrine insufficiency: a case report.

The visceral manifestations of von Hippel-Lindau syndrome rarely are clinically significant until late in the disease process. Pancreatic endocrine insufficiency in the syndrome is extremely uncommon. We report a case of a 32-year-old woman with von Hippel-Lindau syndrome whose initial diagnosis came to light because of a clinical presentation with complications related to pancreatic endocrine insufficiency.

Clinical determinants of abnormalities in pulmonary functions in survivors of the adult respiratory distress syndrome.

Pulmonary function tests (PFTs) were performed in 39 survivors of the adult respiratory distress syndrome (ARDS) in whom clinical data had been prospectively collected during the acute episode. PFTs stabilized within 6 months of the episode and had returned to normal in most survivors. Persistent abnormalities were found after 6 months in diffusing capacity (14 of 23 patients, 61%), vital capacity (10 of 23 patients, 43%), and total lung capacity (five of 24 patients, 21%). To clarify the mechanisms underlying these persistent abnormalities, we attempted to correlate long-term PFT outcomes with estimates of the severity of initial lung injury as assessed from clinical data and with other features of the patient's course. The severity of lung function impairment during the first 3 days of ARDS was not related to long-term PFT values. However, a lower DLCO was related to a higher AaDO2, higher pulmonary artery pressure, and worse radiographic appearance on Days 4 through 7 and to the occurrence of sepsis. A lower FVC was related to higher pulmonary vascular resistance in Days 4 through 7 of ARDS. Long-term values for FVC and TLC were directly related to increasing levels of PEEP applied from Days 4 through 7 of ARDS in patients with peak airway pressures less than 50 cm H2O. Long-term abnormalities of pulmonary function of survivors of ARDS were not related to initial lung impairment but were directly related to persistence of impaired lung function during the acute episode. Recovery of lung function may also have been directly related to therapeutic modalities such as PEEP and impaired by the occurrence of sepsis.

Respiratory effects of high-dose butorphanol.

The effect of butorphanol on respiratory drive was assessed using a carbon dioxide response test (CRT). Eight male volunteers received 3 mg/70 kg of intravenous butorphanol every 30 min to a cumulative dose of 15 mg/70 kg (5 doses). Thirty minutes before the first butorphanol dose, each subject received normal saline to establish a baseline CRT. After each butorphanol dose, a CRT was repeated at 15 min to assess respiratory depression. Minute ventilation was plotted against PaCO2 to generate a regression line for saline and each dose. Slopes and intercepts for each line were calculated by least squares linear regression, and CRT displacement from saline was determined at each dose. The mean slope for each dose was not significantly different from the saline slope (p = 0.23-0.91). The mean displacement (+/- SEM) of the CRT from saline was greatest after the second dose (7.29 +/- 1.94 mm Hg) but not significantly different from the first or subsequent doses (p greater than 0.05). Butorphanol in doses of up to 15 mg/70 kg may have a 'ceiling effect' in respiratory depression.

One hundred percent oxygen lung injury in adult baboons.

Healthy adult baboons exposed to 100% oxygen for 5 to 7 days maintained on continuous mechanical ventilation develop severe bilateral noncardiogenic pulmonary edema that resembles in many aspects the human adult respiratory distress syndrome (ARDS). In the present study, we evaluated the effects of hyperoxia for 5 to 6 days in 8 baboons to compare changes in abnormalities in bronchoalveolar lavage fluid (BALF) biochemical markers, hemodynamic measurements, and pulmonary function tests in order to find early predictors of lung injury. All animals had bilateral alveolar infiltrates, severe hypoxemia, and progressive deterioration of pulmonary function tests. Diffuse alveolar damage and mild-moderate pneumonias were found and were associated with low-grade bacterial infection. Total lung capacity, diffusing capacity for carbon monoxide, pulmonary static compliance, and oxygenation were significantly impaired after Day 5; BALF proteins, elastase, and total polymorphonuclear leukocytes increased significantly at least 24 h before (Day 4) any abnormalities in chest radiographs, pulmonary function tests, and hemodynamic measurements were detected. We conclude that exposure to 100% oxygen in this model causes marked gas exchange, hemodynamic, biochemical, cytologic, radiographic, and pathologic changes similar to those noted in patients with ARDS. Bronchoalveolar lavage abnormalities precede hemodynamic and gas exchange abnormalities.