The effect of two different circuit leaks on the measurement of maximal static inspiratory and expiratory pressures at the mouth (Pimax, Pemax) was assessed in 70 patients with respiratory disease. Patients were divided into three groups with similar anthropometric and spirometric characteristics. The first group (30 patients) had their Pmax measured with a leak of 2.0 mm internal diameter (ID) and 37 mm length (as proposed by T. Ringqvist) and repeated with a second leak of 1.0 mm ID and 15 mm length (as recommended by J. L. Clausen). The two measurements were done in random order. Measurements for the other two groups (20 patients each) were taken with one or another, the two leaks randomly alternated with no leak. Pimax measurements obtained with Ringqvist's leak were 17 percent (p less than 0.005) lower than those with Clausen's leak and 22 percent (p less than 0.005) lower than those with no leak. Pemax measurements performed with Ringqvist's leak in place were 11 percent (p less than 0.005) lower than those with Clausen's leak and 11 percent (p less than 0.005) lower than those obtained with no leak. The comparison between Clausen's leak and no leak showed no statistically significant difference. We conclude that whenever the effect of pressure generated in the mouth is to be avoided in the measurement of respiratory Pmax, a leak of the size proposed by Ringqvist is to be preferred.

To examine the differential effect of drugs used for stress ulcer prophylaxis on nosocomial pneumonia in critically ill patients.

Late recurrent Candida endocarditis (LRCE) developed on a prosthetic mitral valve 22 months after treatment for primary native mitral valve endocarditis. The LRCE was difficult to diagnose; results of two dimensional echocardiography and repeated blood cultures were negative. Only transesophageal echocardiography revealed a vegetation and only lysis centrifugation blood cultures demonstrated candidemia. Postmortem examination revealed a large Candida vegetation on the prosthetic valve and Candida in the mitral valve ring. This case and a review of the literature indicate that Candida endocarditis treated with amphotericin B and prosthetic valve replacement may recur months after treatment, and that LRCE, which is difficult to diagnose and treat, may be best prevented by lifelong antifungal suppressive therapy.

A 50-year-old man with pulmonary fibrosis and COPD presented with worsening cough, dyspnea, chest pain, and hypoxemia of no readily apparent etiology, approximately four weeks after insertion of a transtracheal oxygen therapy catheter. Despite vigorous bronchial hygiene therapy, the patient died. Autopsy revealed obstruction of the trachea by a large mucous ball. We point out the nonspecificity of physical and radiologic findings associated with this condition and suggest that serial flow-volume loop analysis or earlier use of fiberoptic bronchoscopy might have been of assistance in premortem diagnosis of the mucous plug.

The adverse effects of prolonged immobility are due primarily to gravitational effects on blood flow and ventilation, impairment of the normal mucociliary escalator and possibly an increase in extravascular lung water. However, CLRT theoretically should reverse these abnormalities. The sequence of events that culminate in LRTI or pneumonia is unclear; however, low tidal volumes, increased extravascular lung water and the accumulation of bronchopulmonary secretions may lead to atelectasis, a well-known precursor of pneumonia. Three prospective, randomized studies evaluating patients with acute head trauma, orthopedic injuries requiring traction and blunt chest trauma all showed a decreased incidence of LRTI or pneumonia with CLRT compared with those treated in a conventional bed and turned every 2 h by the nursing staff. In general, the methodology was sound with early randomization, use of precise criteria to define LRTI and pneumonia and appropriate observation. The fourth study performed in a medical ICU with a heterogeneous group of patients did not show a difference in incidence of nosocomial pneumonia between treatment in CLRT and a conventional bed, but did show a decreased length of ICU stay for patients with pneumonia treated with CLRT. It appears that if CLRT is to be effective, it needs to be instituted early in the patient's illness. The length of time that CLRT should be utilized is unknown; however, intuitively, as long as the patient is at risk, the therapy should be continued. It is also unclear whether CLRT should be started at full rotation immediately or begun at lesser degrees of rotation and advanced serially over several hours. Another unknown is the minimum time that CLRT should be administered per day. In the studies discussed, most patients were rotated for 10 to 16 h/day. The minimum degree of rotation necessary for an effect is also unknown; in the studies cited, rotations from 40 degrees to 62 degrees in each direction were used. Based on the current data, the early use of CLRT in comatose or otherwise immobile patients decreases the incidence of LRTI including pneumonia over the first 7 to 14 days of ICU care. The prevention of pneumonia and more rapid transfer from the ICU should offset the additional expense of a specialized bed. The data suggest that a multicenter study with accrual of a large number of patients to evaluate this form of therapy in a prospective, randomized study is necessary. If the hypothesis that CLRT decreases the incidence of nosocomial pneumonia in the ICU is proven, the impact on critical care in the 90s would be substantial.

The most common pulmonary complication of EVS is pleural effusion. The most clinically significant pulmonary complication of EVS is delayed perforation with formation of esophagopleural or esophagobronchial fistula. Pneumonia, empyema, pulmonary infarction, and atelectasis can also occur. Endoscopic variceal sclerotherapy probably does not cause ARDS, but that issue remains unsettled. Transient relative pulmonary hypertension during EVS is probably of no clinical significance, but caution is urged when sclerosing varices in a patient with borderline right heart function.

The modern treatment of cardiopulmonary disease is increasingly predicated on the goal of dissolving the offending clot to establish vascular patency as rapidly as possible and then preventing rethrombosis. The availability of thrombolytic agents has made this therapeutic approach possible and the adjunctive use of heparin, coumarin, and aspirin has increased the efficacy of lytic drugs. The administration of any of these medications is associated with inherent risks, which are enhanced when they are used concomitantly. An understanding of coagulation and an appreciation of the pathophysiologic processes of the thrombotic events occurring in cardiopulmonary disease states are critical to the formulation of innovative therapeutic regimens that maximize efficacy and safety. Furthermore, knowledge of the comparative pharmacology of the various thrombolytic agents is useful in explaining the benefits and complications observed in clinical trials.

During the past year, there have been 2 major advances in the management of pulmonary embolism (PE). First, the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) investigators published the results of their comparison of ventilation-perfusion lung scanning and pulmonary angiography. This multimillion-dollar trial sponsored by the National Heart, Lung, and Blood Institute indicated that lung scanning is surprisingly insensitive to the diagnosis of PE. High-probability lung scanning detects fewer than half of the cases of PE that are found at pulmonary angiography. The PIOPED results force us to conclude that increased utilization of both ultrasonography of the deep leg veins and pulmonary angiography is warranted in order to detect the majority of cases of venous thromboembolism. Second, in June 1990, the Food and Drug Administration approved recombinant human tissue-type plasminogen activator (rt-PA) for use in the treatment of acute PE. The dosing regimen is 100 mg of rt-PA as a continuous peripheral intravenous infusion administered over 2 h. The convenience, rapid effect, and relative safety of this therapeutic approach may result in increased use of thrombolysis for management of PE.

The diagnosis of lower limb deep vein thrombosis can be made rapidly by compression ultrasound. This noninvasive test has almost completely replaced contrast phlebography in some major hospitals in North America. Compression ultrasound is well suited for making the diagnosis of deep vein thrombosis, measuring its extent, and monitoring the draining veins of the calf for evidence of spread of calf vein thrombosis. The nature of the deep vein thrombus, whether it is obstructing or nonobstructing, can be determined with the additional use of color Doppler mapping, a technique that displays flowing blood as a color overlay to the 2-dimensional real-time ultrasound image. Serial noninvasive determinations of the extent of thrombus in the lower-extremity deep veins is now possible with this combined sonographic imaging approach. Monitoring of possible changes in the extent of the thrombus burden can now be undertaken in patients enrolled in trials assessing the efficacy of different thrombolytic regimens.

A canine model of pulmonary embolism, induced by injection of autologous radioactive blood clots, was used to investigate principles of thrombolysis in pulmonary embolism. One study compared recombinant tissue plasminogen activator (rtPA) with heparin in the treatment of pulmonary embolism. This study also compared the efficacy of rtPA (1 mg/kg) given over 15 min (rtPA15) to the same total dose infused over 90 min. Compared with heparin, both rtPA regimens induced marked pulmonary thrombolysis. During drug infusion, the rate of thrombolysis was increased 2-fold with rtPA15. A 2nd canine study investigated the physiologic mechanism of the decrease in pulmonary artery pressure with rtPA. The pattern of hemodynamic improvement with rtPA indicated that pulmonary thrombolysis predominantly occurred in partially, rather than totally, obstructed vascular units. A 3rd canine study compared rtPA and high-dose urokinase (UK) in treatment of pulmonary embolism. Both rtPA regimens were superior to UK in inducing pulmonary thrombolysis and improving pulmonary hemodynamics. Most recently, the effects of flow dynamics on rtPA-induced pulmonary thrombolysis were investigated, and it was demonstrated that an increase in cardiac output markedly enhanced rtPA-induced pulmonary thrombolysis. Most likely, the increase in cardiac output increased thrombolysis by enhancing delivery of rtPA to thrombus in partially obstructed vascular units.

Emergency cardiac catheterization and coronary angioplasty for acute myocardial infarction (MI) have a continuing role in the thrombolytic era. Although thrombolytic therapy has revolutionized the treatment of MI, it has significant shortcomings: about 75% of patients with acute MI cannot be treated with thrombolytic agents, 25% of treated patients will have persistent occlusion of the infarct-related artery, 70% will have a residual stenosis greater than or equal to 70%, and 20% of treated patients will experience reocclusion. Cardiac catheterization identifies the coronary anatomy for mechanical revascularization and allows the unstable patient to receive special therapy, such as intra-aortic balloon pumping. Many large clinical studies have evaluated approaches to coronary angioplasty for acute MI. Deferred angioplasty has indisputable advantages over immediate routine angioplasty. Direct angioplasty without concomitant thrombolytic therapy has acceptable success and complication rates, so that it can be considered the treatment of choice for acute MI in centers with an angioplasty program if thrombolytic therapy is contraindicated. Patients at very low risk may not require cardiac catheterization routinely before discharge, since their good prognosis cannot be improved by invasive evaluation and intervention. Emergency surgical revascularization is indicated in a very small percentage of cases.

The beneficial effects of coronary thrombolytic therapy may be enhanced by certain adjunctive therapies. Some of these are of proven value, some appear to offer no benefit in spite of theoretical advantages, and some remain to be evaluated in clinical trials. Acetylsalicylic acid markedly enhances the mortality reduction of thrombolytic therapy and should be used routinely. There is a strong theoretical rationale for the use of heparin, but evidence for its benefit exists primarily in small angiographic trials, and convincing clinical benefit has not yet been demonstrated. Early intravenous beta-blockers were shown in the prethrombolysis era to confer modest benefit, but extensive data on their adjuvant use with thrombolysis are available from only one trial. Intravenous nitrates were demonstrated to reduce mortality in the prethrombolysis era, and are soon to be evaluated in trials employing thrombolytic therapy. The calcium channel blockers, in spite of a variety of theoretical benefits, have proved to be of no value acutely, and in the subacute setting, only diltiazem appears to confer benefit in the subgroup of patients with non-O-wave infarction. Angiotensin-converting enzyme inhibitors are likely to be of value in survivors of acute myocardial infarction with left ventricular dysfunction, and benefits observed with acute use in experimental infarction are now being evaluated in clinical trials.