John G. Weg

The Clinical Course of Pulmonary Embolism

BACKGROUND Pulmonary embolism is a potentially fatal disorder. Information about the outcome of clinically recognized pulmonary embolism is sparse, particularly given that new treatments for more seriously ill patients are now available. METHODS We prospectively followed 399 patients with pulmonary embolism diagnosed by lung scanning and pulmonary angiography, who were enrolled in a multicenter diagnostic trial. We reviewed all hospitalizations, all new investigations of pulmonary embolism, and all deaths among the patients within one year of diagnosis. RESULTS Of the 399 patients, 375 (94 percent) received treatment for pulmonary embolism, usually conventional anticoagulation. Only 10 patients (2.5 percent) died of pulmonary embolism; 9 of them had clinically suspected recurrent pulmonary embolism. Clinically apparent pulmonary embolism recurred in 33 patients (8.3 percent), of whom 45 percent died during follow-up. Ninety-five patients with pulmonary embolism (23.8 percent) died within one year. The conditions associated with these deaths were cancer (relative risk, 3.8; 95 percent confidence interval, 2.3 to 6.4), left-sided congestive heart failure (relative risk, 2.7; 95 percent confidence interval, 1.5 to 4.6), and chronic lung disease (relative risk, 2.2; 95 percent confidence interval, 1.2 to 4.0). The most frequent causes of death in patients with pulmonary embolism were cancer (in 34.7 percent), infection (22.1 percent), and cardiac disease (16.8 percent). CONCLUSIONS When properly diagnosed and treated, clinically apparent pulmonary embolism was an uncommon cause of death, and it recurred in only a small minority of patients. Most deaths were due to underlying diseases. Patients with pulmonary embolism who had cancer, congestive heart failure, or chronic lung disease had a higher risk of dying within one year than did other patients with pulmonary embolism.

Complications and validity of pulmonary angiography in acute pulmonary embolism.

BackgroundThe Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED. Methods and ResultsComplications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p<0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74±13 years versus 57±17 years (p<0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%. ConclusionsThe risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk.

Aerosolized Surfactant in Adults with Sepsis-Induced Acute Respiratory Distress Syndrome

BACKGROUND Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival. METHODS We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiological and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter, 364 patients) or placebo (o.45 percent saline; 361 patients) in aerosolized form for up to five days. RESULTS The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (+/- SD) age was 50 +/- 17 years in the surfactant group and 53 +/- 18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4 +/- 25 and 70.5 +/- 25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups. CONCLUSIONS The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function.

DIAGNOSIS OF PULMONARY EMBOLISM WITH MAGNETIC RESONANCE ANGIOGRAPHY

BACKGROUND Diagnosing pulmonary embolism may be difficult, because there is no reliable noninvasive imaging method. We compared a new noninvasive method, gadolinium-enhanced pulmonary magnetic resonance angiography, with standard pulmonary angiography for diagnosing pulmonary embolism. METHODS A total of 30 consecutive patients with suspected pulmonary embolism underwent both standard pulmonary angiography and magnetic resonance angiography during the pulmonary arterial phase at the time of an intravenous bolus of gadolinium. All magnetic resonance images were reviewed for the presence or absence of pulmonary emboli by three independent reviewers who were unaware of the findings on standard angiograms. RESULTS Pulmonary embolism was detected by standard pulmonary angiography in 8 of the 30 patients in whom pulmonary embolism was suspected. All 5 lobar emboli and 16 of 17 segmental emboli identified on standard angiograms were also identified on magnetic resonance images. Two of the three reviewers reported one false positive magnetic resonance angiogram each. As compared with standard pulmonary angiography, the three sets of readings had sensitivities of 100, 87, and 75 percent and specificities of 95, 100, and 95 percent, respectively. The interobserver correlation was good (k=0.57 to 0.83 for all vessels, 0.49 to 1.0 for main and lobar vessels, and 0.40 to 0.81 for segmental vessels). CONCLUSIONS In this preliminary study, gadolinium-enhanced magnetic resonance angiography of the pulmonary arteries, as compared with conventional pulmonary angiography, had high sensitivity and specificity for the diagnosis of pulmonary embolism. This new technique shows promise as a noninvasive method of diagnosing pulmonary embolism without the need for ionizing radiation or iodinated contrast material.

Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism: A Multicenter Prospective Study (PIOPED III)

BACKGROUND The accuracy of gadolinium-enhanced magnetic resonance pulmonary angiography and magnetic resonance venography for diagnosing pulmonary embolism has not been determined conclusively. OBJECTIVE To investigate performance characteristics of magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism. DESIGN Prospective, multicenter study from 10 April 2006 to 30 September 2008. SETTING 7 hospitals and their emergency services. PATIENTS 371 adults with diagnosed or excluded pulmonary embolism. MEASUREMENTS Sensitivity, specificity, and likelihood ratios were measured by comparing independently read magnetic resonance imaging with the reference standard for diagnosing pulmonary embolism. Reference standard diagnosis or exclusion was made by using various tests, including computed tomographic angiography and venography, ventilation-perfusion lung scan, venous ultrasonography, d-dimer assay, and clinical assessment. RESULTS Magnetic resonance angiography, averaged across centers, was technically inadequate in 25% of patients (92 of 371). The proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 57% (59 of 104) with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. LIMITATION A high proportion of patients with suspected embolism was not eligible or declined to participate. CONCLUSION Magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Magnetic resonance pulmonary angiography and magnetic resonance venography combined have a higher sensitivity than magnetic resonance pulmonary angiography alone in patients with technically adequate images, but it is more difficult to obtain technically adequate images with the 2 procedures.

The Relation of Pneumothorax and Other Air Leaks to Mortality in the Acute Respiratory Distress Syndrome

BACKGROUND In patients with the acute respiratory distress syndrome, pneumothorax and other air leaks - any extrusion of air outside the tracheobronchial tree - have been attributed to high ventilatory pressures or volumes and linked to increased mortality. METHODS We analyzed data from a prospective trial of aerosolized synthetic surfactant in 725 patients with the acute respiratory distress syndrome induced by sepsis. We compared the ventilatory pressures and volumes in the patients without any air leaks (the highest values during the five-day study) with the pressures and volumes in those with pneumothorax or with any air leaks (the highest values during the 16- and 24-hour periods before the complication developed). RESULTS Fifty patients (6.9 percent) had pneumothorax and 77 (10.6 percent) had pneumothorax or other air leaks. There were no significant differences between patients with air leaks and those without air leaks in any pressure or volume examined. Overall mortality at 30 days was 40.0 percent (95 percent confidence interval, 36.4 to 43.6); among the patients with pneumothorax, it was 46.0 percent (95 percent confidence interval, 32.2 to 59.8), and among those without pneumothorax, it was 39.3 percent (95 percent confidence interval, 35.6 to 43.0; P=0.35). The mortality rate was 45.5 percent (95 percent confidence interval, 34.4 to 56.6) in the group with any air leaks and 39.0 percent (95 percent confidence interval, 35.3 to 42.8) in the group without air leaks (P=0.28). CONCLUSIONS In patients with sepsis-induced acute respiratory distress syndrome who were receiving mechanical ventilation with conventional pressures and volumes, there were no significant correlations between high ventilatory pressures or volumes and the development of pneumothorax or other air leaks. Pneumothorax or other air leaks were not associated with a significantly increased mortality rate.

Clinical Characteristics of Patients with Acute Pulmonary Embolism

Abstract Among 117 patients with pulmonary embolism (PE) and no prior cardiac or pulmonary disease who participated in the National Heart, Lung, and Blood Institute Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, combinations of clinical characteristics were identified that were present in nearly all in whom the diagnosis of PE was made. 1 We now assess these as well as additional combinations of characteristics in the entire population of patients with acute PE who participated in PIOPED, irrespective of the presence of prior cardiopulmonary disease.

Enlarged Right Ventricle Without Shock in Acute Pulmonary Embolism: Prognosis

OBJECTIVE An unsettled issue is the use of thrombolytic agents in patients with acute pulmonary embolism (PE) who are hemodynamically stable but have right ventricular (RV) enlargement. We assessed the in-hospital mortality of hemodynamically stable patients with PE and RV enlargement. METHODS Patients were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis II. Exclusions included shock, critical illness, ventilatory support, or myocardial infarction within 1 month, and ventricular tachycardia or ventricular fibrillation within 24 hours. We evaluated the ratio of the RV minor axis to the left ventricular minor axis measured on transverse images during computed tomographic angiography. RESULTS Among 76 patients with RV enlargement treated with anticoagulants and/or inferior vena cava filters, in-hospital deaths from PE were 0 of 76 (0%) and all-cause mortality was 2 of 76 (2.6%). No septal motion abnormality was observed in 49 patients (64%), septal flattening was observed in 25 patients (33%), and septal deviation was observed in 2 patients (3%). No patients required ventilatory support, vasopressor therapy, rescue thrombolytic therapy, or catheter embolectomy. There were no in-hospital deaths caused by PE. There was no difference in all-cause mortality between patients with and without RV enlargement (relative risk=1.04). CONCLUSION In-hospital prognosis is good in patients with PE and RV enlargement if they are not in shock, acutely ill, or on ventilatory support, or had a recent myocardial infarction or life-threatening arrhythmia. RV enlargement alone in patients with PE, therefore, does not seem to indicate a poor prognosis or the need for thrombolytic therapy.

Gadolinium-Enhanced Magnetic Resonance Angiography for Detection of Acute Pulmonary Embolism: An In-depth Review

STUDY OBJECTIVE To review the published experience with gadolinium-enhanced magnetic resonance angiography (MRA) for the detection of acute pulmonary embolism (PE) in order to test the hypothesis that gadolinium-enhanced MRA may be potentially sensitive and specific enough to include it among diagnostic alternatives in the evaluation of patients with suspected PE. METHODS Studies were identified by searching MEDLINE for trials that used gadolinium-enhanced MRA to diagnose acute PE based on the visualization of an intraluminal filling defect or a cutoff vessel, using pulmonary angiography as a reference standard. RESULTS Twenty-eight investigations were identified in which MRA was used to diagnose PE. Only three studies, however, met the criteria for inclusion in the analysis. In these three case series, the sensitivity of gadolinium-enhanced MRA ranged from 77 to 100%, and the specificity ranged from 95 to 98%. CONCLUSION Gadolinium-enhanced MRA may be a useful diagnostic alternative in some patients with suspected acute PE, particularly if they have an elevated creatinine level, have an allergy to radiographic contrast material, or should, if possible, avoid exposure to ionizing radiation.

Respiratory Stimulation with Intravenous Doxapram in Respiratory Failure

Abstract The ability of a respiratory stimulant (doxapram) to maintain arterial carbon dioxide tension and pH within narrow limits during oxygen administration was assessed in a double-blind study of 78 patients with chronic obstructive lung disease admitted to hospitals for management of acute respiratory failure. The first two hours after admission constituted the study period, with either doxapram or placebo being given intravenously (2 to 3 mg per minute). During the two-hour period, oxygen administration was associated with elevation of carbon dioxide tension or decline in pH (or both) beyond the desired range in 36.8 per cent of the patients receiving placebo, but in only 17.5 per cent of those receiving doxapram. The results suggest that doxapram may prove a useful adjunct in the management of patients in whom oxygen therapy may be expected to exaggerate hypercapnia and acidosis.