The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation.

Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.

Emotional well-being of living kidney donors: findings from the RELIVE Study.

Following kidney donation, short-term quality of life outcomes compare favorably to US normative data but long-term effects on mood are not known. In the Renal and Lung Living Donors Evaluation Study (RELIVE), records from donations performed 1963-2005 were reviewed for depression and antidepressant use predonation. Postdonation, in a cross-sectional cohort design 2010-2012, donors completed the Patient Health Questionnaire (PHQ-9) depression screening instrument, the Life Orientation Test-Revised, 36-Item Short Form Health Survey and donation experience questions. Of 6909 eligible donors, 3470 were contacted and 2455 participated (71%). The percent with depressive symptoms (8%; PHQ-9>10) was similar to National Health and Nutrition Examination Survey participants (7%, p=0.30). Predonation psychiatric disorders were more common in unrelated than related donors (p=0.05). Postdonation predictors of depressive symptoms included nonwhite race OR=2.00, p=0.020), younger age at donation (OR=1.33 per 10 years, p=0.002), longer recovery time from donation (OR=1.74, p=0.0009), greater financial burden (OR=1.32, p=0.013) and feeling morally obligated to donate (OR=1.23, p=0.003). While cross-sectional prevalence of depression is comparable to population normative data, some factors identifiable around time of donation, including longer recovery, financial stressors, younger age and moral obligation to donate may identify donors more likely to develop future depression, providing an opportunity for intervention.

Morbidity and mortality of live lung donation: results from the RELIVE study.

The Renal and Lung Living Donors Evaluation Study assesses outcomes of live lung (lobectomy) donors. This is a retrospective cohort study at University of Southern California (USC) and Washington University (WASHU) Medical Centers (1993­2006), using medical records to assess morbidity and national databases to ascertain postdonation survival and lung transplantation. Serious complications were defined as those that required significant treatment, were potentially life-threatening or led to prolonged hospitalization. The 369 live lung donors (287 USC, 82 WASHU) were predominantly white, non-Hispanic and male; 72% had a biological relationship to the recipient, and 30% were recipient parents. Serious complications occurred in 18% of donors; 2.2% underwent reoperation and 6.5% had an early rehospitalization. The two centers had significantly different incidences of serious complications (p < 0.001). No deaths occurred and no donors underwent lung transplantation during 4000+ person-years of follow-up (death: minimum 4, maximum 17 years; transplant: minimum 5, maximum 19). Live lung donation remains a potential option for recipients when using deceased donor lungs lacks feasibility. However, the use of two live donors for each recipient and the risk of morbidity associated with live lung donation do not justify this approach when deceased lung donors remain available. Center effects and long-term live donor outcomes require further evaluation.

The shock index and the simplified PESI for identification of low-risk patients with acute pulmonary embolism.

We compared the test characteristics of the shock index (SI) and the simplified pulmonary embolism severity index (sPESI) for predicting 30-day outcomes in a cohort of 1,206 patients with objectively confirmed pulmonary embolism (PE). The primary outcome of the study was all-cause mortality. The secondary outcome was nonfatal symptomatic recurrent venous thromboembolism (VTE) or nonfatal major bleeding. Overall, 119 (9.9%) out of 1,206 patients died (95% CI 8.2-11.5%) during the first month of follow-up. The sPESI classified fewer patients as low-risk (369 (31%) out of 1,206 patients, 95% CI 28-33%) compared to the SI (1,024 (85%) out of 1,206 patients, 95% CI 83-87%) (p<0.001). Low-risk patients based on the sPESI had a lower 30-day mortality than those based on the SI (1.6% (95% CI 0.3-2.9%) versus 8.3% (95% CI 6.6-10.0%)), while the 30-day rate of nonfatal recurrent VTE or major bleeding was similar (2.2% (95%CI 0.7-3.6%) versus 3.3% (95%CI 2.2-4.4%)). The net reclassification improvement with the sPESI was 13.4% (p = 0.07). The integrated discrimination improvement was estimated as 1.8% (p<0.001). The sPESI quantified the prognosis of patients with PE better than the SI.

Lung transplantation in the United States, 1999-2008.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1999 to 2008. While adult lung transplantation grew significantly over the past decade, rates of heart-lung and pediatric lung transplantation have remained low. Since implementation of the lung allocation score (LAS) donor allocation system in 2005, decreases in the number of active waiting list patients, waiting times for lung transplantation and death rates on the waiting list have occurred. However, characteristics of recipients transplanted in the LAS era differed from those transplanted earlier. The proportion of candidates undergoing lung transplantation for chronic obstructive pulmonary disease decreased, while increasing for those with pulmonary fibrosis. In the LAS era, older, sicker and previously transplanted candidates underwent transplantation more frequently compared with the previous era. Despite these changes, when compared with the pre-LAS era, 1-year survival after lung transplantation did not significantly change after LAS inception. The long-term effects of the change in the characteristics of lung transplant recipients on overall outcomes for lung transplantation remain unknown. Continued surveillance and refinements to the LAS system will affect the distribution and types of candidates transplanted and hopefully lead to improved system efficiency and outcomes.

Lung transplantation in the United States, 1998-2007.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.

Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome.

Primary graft dysfunction (PGD) is a common early complication after lung transplantation. We conducted a retrospective cohort study of 334 recipients to evaluate the impact of PGD graded at 24, 48 and 72 h on the risk of bronchiolitis obliterans syndrome (BOS) development (stage 1) and progression (stages 2 and 3). We constructed multivariable Cox proportional hazards models to determine the risk of BOS attributable to PGD in the context of other potential risk factors including acute rejection, lymphocytic bronchitis and respiratory viral infections. All grades of PGD at all time points were significant risk factors for BOS development and progression independent of acute rejection, lymphocytic bronchitis and respiratory viral infections. Specifically, PGD grade 1 at T24 was associated with a relative risk of BOS stage 1 of 1.93, grade 2 with a relative risk of 2.29 and grade 3 with a relative risk of 3.31. Furthermore, this direct relationship between the severity of PGD and the risk of BOS persisted at all time points. We conclude that all grades of PGD at all time points are independent risk factors for BOS development and progression. Future strategies that might attenuate the severity of PGD may mitigate the risk of BOS.

Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism.

The assessment of risk and appropriate treatment of patients with acute pulmonary embolism (PE) remains a challenge. The prognostic performance of cardiac troponin I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in consecutive haemodynamically stable patients with PE. The present study included 318 haemodynamically stable patients with PE. During the 30-day study period, 23 (7%) patients died. cTnI was elevated (>or=0.1 ng x mL(-1)) in 102 (32%) patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of illness assessed using the PE severity index (PESI) were significantly associated with an increased risk for mortality, but no significant association was found between elevation of cTnI and 30-day mortality in a logistic regression analysis. When only fatal PE was considered, multivariate analysis showed that severity of illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence interval (CI) 1.1-12.8) were associated with a significant increase in the risk for death. The negative predictive value (95% CI) of a negative cTnI for mortality was 93 (90-97)%. In conclusion, in haemodynamically stable patients with acute pulmonary embolism, cardiac troponin I was not an independent predictor of 30-day all-cause mortality, although it did predict fatal pulmonary embolism.

Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism.

UNLABELLED: ESSENTIALS: When high probability of pulmonary embolism (PE), sensitivity of computed tomography (CT) is unclear. We investigated the sensitivity of multidetector CT among 134 patients with a high probability of PE. A normal CT alone may not safely exclude PE in patients with a high clinical pretest probability. In patients with no clear alternative diagnosis after CTPA, further testing should be strongly considered. BACKGROUND: Whether patients with a negative multidetector computed tomographic pulmonary angiography (CTPA) result and a high clinical pretest probability of pulmonary embolism (PE) should be further investigated is controversial. METHODS: This was a prospective investigation of the sensitivity of multidetector CTPA among patients with a priori clinical assessment of a high probability of PE according to the Wells criteria. Among patients with a negative CTPA result, the diagnosis of PE required at least one of the following conditions: ventilation/perfusion lung scan showing a high probability of PE in a patient with no history of PE, abnormal findings on venous ultrasonography in a patient without previous deep vein thrombosis at that site, or the occurrence of venous thromboembolism (VTE) in a 3-month follow-up period after anticoagulation was withheld because of a negative multidetector CTPA result. RESULTS: We identified 498 patients with a priori clinical assessment of a high probability of PE and a completed CTPA study. CTPA excluded PE in 134 patients; in these patients, the pooled incidence of VTE was 5.2% (seven of 134 patients; 95% confidence interval [CI] 1.5-9.0). Five patients had VTEs that were confirmed by an additional imaging test despite a negative CTPA result (five of 48 patients; 10.4%; 95% CI 1.8-19.1), and two patients had objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months (two of 86 patients; 2.3%; 95% CI 0-5.5). None of the patients had a fatal PE during follow-up. CONCLUSIONS: A normal multidetector CTPA result alone may not safely exclude PE in patients with a high clinical pretest probability.

Cost for inpatient care of venous thrombosis: a trial of enoxaparin vs standard heparin.

BACKGROUND: Enoxaparin, a low-molecular-weight heparin administered to hospitalized patients once or twice daily, has shown efficacy and safety equivalent to unfractionated heparin in the treatment of acute venous thromboembolic disease. Although the cost of either enoxaparin regimen is greater than that of unfractionated heparin, the overall cost of care for each of these 3 treatment strategies is unknown. METHODS: A cost minimization analysis of a 3-month, partially blinded, randomized, controlled efficacy and safety trial of anticoagulant therapy for deep vein thrombosis. Three hundred thirty-nine hospitalized patients with symptomatic lower extremity deep vein thrombosis were randomly assigned to initial therapy with subcutaneous enoxaparin either once (n = 112) or twice (n = 123) daily, or with dose-adjusted intravenous unfractionated heparin (n = 104), followed by long-term oral anticoagulant therapy. Estimated 1997 total cost from a third-party payer perspective for the 3-month episode of care was calculated by assigning standard unit costs to counts of medical resources used by each patient in the clinical trial. RESULTS: Average total cost for the 3-month episode of care was similar across all 3 treatment regimens: once-daily dose of enoxaparin, $12,166 (95% confidence interval [CI], $10,744-$13,588); twice-daily dose of enoxaparin, $11,558 (95% CI, $10,201-$12,915); and unfractionated heparin, $12,146 (95% CI, $10,670-$12,622). Bootstrapped estimates and sensitivity analyses did not significantly change findings. CONCLUSIONS: There was no significant difference in the overall cost for the 3-month episode of care for patients treated with either enoxaparin or unfractionated heparin. Additional acquisition costs for anticoagulant medication among patients treated with enoxaparin were offset by savings associated with lower incidence of hospital readmission and shorter duration of venous thromboembolism-related readmissions.

Acute respiratory failure due to extramedullary hematopoiesis.

Extramedullary hematopoiesis (EMH) associated with myelofibrosis uncommonly occurs within the thorax. We describe the first reported case of acute and rapidly fatal respiratory failure due to pulmonary interstitial EMH associated with myelofibrosis. Interstitial EMH should be considered in the differential diagnosis of patients with interstitial pulmonary infiltrates and respiratory failure accompanying a disease process known to predispose to the development of EMH.

Modification of pleural fluid pH by local anesthesia.

BACKGROUND: It is a common practice to anesthetize patients before performing a thoracentesis. We postulated that this technique may cause a clinically significant difference in the pH of the pleural fluid. METHODS: We compared two methods of determining pleural fluid pH. Fifty patients undergoing diagnostic or therapeutic thoracentesis were enrolled. Two 4-mL aliquots of pleural fluid were anaerobically collected into blood gas syringes containing heparin, one before (group A) and the other after (group B) anesthetizing the patient with 5 mL of 2% mepivacaine. pH was then determined on both samples using an arterial blood gas machine. Agreement analysis was performed overall and in subcategories of pH used to define complicated (<7.1), borderline (7.1 to 7.3), or uncomplicated (>7.3) parapneumonic effusions. We analyzed these same data stratified by the volume of pleural fluid in relationship to the size of the hemithorax (<15% and >15%). RESULTS: There was a statistical difference between the mean pH in both groups (group A, 7.32; group B, 7.28; p<0.0001). There was a significant correlation between the two measures (r = 0.97; p<0.0001). Using the pH subcategories, there was 45% discordance in classification for patients with parapneumonic effusions. The pH values obtained in group B wrongly predicted whether the patient required a chest tube in two of four cases (50%). In patients with effusions that occupied <15% of the affected hemithorax, there was an 80% discordance in classification for patients with parapneumonic effusions, and the pH values obtained in group B wrongly predicted whether the patient required a chest tube in two of two cases (100%). CONCLUSIONS: Local anesthesia is typically used before thoracentesis is performed. However, in cases of suspected parapneumonic effusions that occupy <15% of the affected hemithorax, pH results may be significantly altered by use of local mepivacaine anesthesia.

Patient selection for lung volume reduction surgery: An objective model based on prior clinical decisions and quantitative CT analysis.

OBJECTIVES: We used whole-lung quantitative CT analysis (QCT)-an objective method of evaluating emphysema severity and distribution based on measurement of lung density-to determine whether subjective selection criteria for lung volume reduction surgery are applied consistently and to model the patient selection process, and assessed the relationship of the model to postoperative outcome. DESIGN: Logistic regression analysis using QCT indexes of emphysema and preoperative physiologic test results as the independent variables, and the decision to operate as the dependent variable. SETTING: University hospital. PATIENTS: Seventy patients selected for bilateral lung volume reduction surgery and 32 otherwise operable patients excluded from surgery based on subjective assessment of emphysema morphology on chest radiography, CT, and perfusion scintigraphy. INTERVENTION: Bilateral lung volume reduction surgery in the selected group. MEASUREMENTS AND RESULTS: Emphysema in patients selected for surgery was more severe overall and in the upper lungs by multiple QCT indexes (p < 0.01, unpaired two-tailed t test). Physiologic abnormalities were slightly more severe in selected patients (p < 0.05, unpaired two-tailed t test). The range of many QCT and physiologic values overlapped considerably between the selected and excluded groups. The percent severe emphysema (<- 960 Hounsfield units [HU]), upper/lower lung emphysema ratio (- 900 HU threshold), and residual volume were the key variables in the model predicting selection decisions (model r(2) = 0.48; p < 0.0001). The model correctly predicted selection decisions in 87% of all cases, 91% of the selected group, and 78% of the excluded group. Surgical patients with a higher model-derived probability of selection had greater postoperative improvement in FEV(1) and 6-min walk distance. CONCLUSIONS: Radiologic selection criteria are applied consistently to the majority of patients. QCT features are strongly associated with selection decisions, are related to outcome, and may help improve consistency and confidence in patient selection.

Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema.

Between January 1993 and February 1996, we performed 150 bilateral lung volume reduction procedures for patients with severe emphysema. Patients were selected on the basis of severe dyspnea, increased lung capacity, and a pattern of emphysema that included regions of severe destruction, hyperinflation, and poor perfusion. Twenty percent to 30% of the volume of each lung was excised with the use of a linear stapler and bovine pericardial strips attached to buttress the staple line. Patients were between 36 and 77 years old, with an average 1-second forced expiratory volume of 25% of predicted, total lung capacity of 142% of predicted, and residual volume of 283% of predicted. Ninety-three percent of patients required supplemental oxygen, continuously or with exertion. All patients but one were extubated at the end of the procedure. The 90-day mortality was 4%. Hospital stay progressively decreased with experience, and for the last 50 patients the median hospital stay was 7 days. Prolonged air leakage was the major complication. Results at 6 months show a 51% increase in the 1-second forced expiratory volume and a 28% reduction in the residual volume. The Pao2 increased by an average of 8 mm Hg, and 70% of the patients who had previously required continuous supplemental oxygen no longer had this requirement. The improvements in measured pulmonary function were paralleled by a significant reduction in dyspnea and an improvement in the quality of life. Reevaluation at 1 year and 2 years after operation showed the benefit to be well maintained. We conclude that lung volume reduction offers benefits not achievable by any means other than lung transplantation for highly selected patients with severe emphysema.

Outcome of bilateral lung volume reduction in patients with emphysema potentially eligible for lung transplantation.

OBJECTIVE: Between January 1993 and May 1998, we performed 200 consecutive bilateral lung volume reduction operations. After initial assessment, 99 of these patients were eligible for lung volume reduction and potentially eligible for immediate or eventual lung transplantation on the basis of age and absence of contraindications. All chose to proceed with lung volume reduction surgery. The outcomes of these 99 patients are reviewed to assess the consequences of proceeding with lung volume reduction surgery on patients potentially eligible for lung transplantation. METHODS: A retrospective study was performed with the use of a prospectively assembled computer database. RESULTS: The 61 men and 38 women were 55 +/- 7 years old at evaluation for lung volume reduction. Mean values for first second expired volume, total lung capacity, and residual volume were 24% +/- 8%, 141% +/- 19%, and 294% +/- 54% predicted. There were 4 operative deaths and 17 late deaths. Two-year and 5-year survival after evaluation for lung volume reduction are 92% and 75%. The 32 patients who have been listed for transplantation after lung volume reduction include 15 who have undergone transplantation, 14 who remain on the list, and 3 who have been removed from the list. All 15 transplant recipients survived transplantation and 3 have subsequently died of rejection or late infection. The 12 living recipients have a median post-transplantation follow-up of 1.7 years. The age at transplantation was 58 +/- 5 years with transplantation occurring 3.8 +/- 1.1 years after lung volume reduction. Sixteen of 99 patients underwent lower lobe volume reduction with an increased rate of listing (63%, P =.008) and transplantation (38%, P =.003) compared with patients undergoing upper lobe volume reduction. Patients listed for transplantation were younger, more impaired, and experienced less benefit from lung volume reduction than patients not yet listed for transplantation. CONCLUSIONS: The preliminary use of lung volume reduction in patients potentially suitable for transplantation does not appear to jeopardize the chances for subsequent successful transplantation.

Criteria for outpatient management of proximal lower extremity deep venous thrombosis.

STUDY OBJECTIVES: To develop and to evaluate selection criteria for outpatient management of deep venous thrombosis (DVT). DESIGN: We developed outpatient treatment eligibility criteria that incorporated demographic and clinical data. We aimed to exclude patients at high risk for bleeding or recurrent clotting, as well as those with pulmonary embolism, limited cardiopulmonary reserve, or need for hospitalization due to another illness. Then, we retrospectively applied the criteria to hospitalized patients with newly diagnosed proximal lower extremity DVT to determine the fraction of patients eligible for outpatient therapy; patients were classified as eligible, possibly eligible, or ineligible for home treatment based on the selection criteria. SETTING: University hospital. PATIENTS: One hundred ninety-five hospitalized patients diagnosed as having proximal lower extremity DVT by duplex ultrasound over a 1-year period. MEASUREMENTS: Frequency of complications during initial DVT therapy, including major bleeding, symptomatic thromboembolism, and death. RESULTS: Eighteen (9%) patients were classified as eligible, and 18 (9%) were classified as possibly eligible for outpatient therapy. None of these patients developed complications. Of the 159 (82%) patients classified as ineligible, 13 (8%; 95% confidence interval [CI], 4 to 12%) died or developed serious complications. Therefore, the eligibility criteria had a sensitivity of 100% (95% CI, 92 to 100%) and a negative predictive value of 100% (95% CI, 92 to 100%) for predicting serious complications. CONCLUSIONS: Specific eligibility criteria may identify a subset of patients with acute DVT who can be treated safely at home.

Lung volume reduction surgery for emphysema.

There has been dramatic resurgence of interest in surgical treatment of emphysema, particularly "lung volume reduction" procedures. Recent studies have demonstrated improvements in pulmonary function, lung mechanics, exercise tolerance, and quality of life in selected patients following volume reduction procedures. However, considerable uncertainty remains regarding overall benefit, optimal patient selection, operative techniques, and duration of response. This summarizes current approaches to lung volume reduction surgery, available clinical outcome information, selection criteria, and physiologic mechanisms of response, and discusses the potential role for surgical volume reduction in treatment of emphysema. Recent data appear to support the efficacy of bilateral staple lung volume reduction surgery in patients with severe symptomatic heterogeneously distributed emphysema. Further studies will be needed to determine relative value of different operative techniques and benefit in patients with other clinical presentations.

The efficacy of blood cardioplegia is not due to oxygen delivery.

Twenty-seven canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work and myocardial oxygen consumption during incremental volume loading on right heart bypass before and 30 minutes after 2 hours of cardioplegic arrest at 10 degrees C. Three cardioplegic solutions were used: Hematocrit values were 17.0% (group I), 8.2% (group II), and 0% (group III). In all groups the slope of the linear stroke work versus end-diastolic volume relationship, a measure of contractility, was unchanged after ischemic arrest. However, the myocardial oxygen consumption for basal metabolism was increased an average of 25.5% after arrest with plasma (group III). Since the plasma concentration in all three groups was identical, and the oxygen available to the hearts during ischemia was the same in groups II and III, the efficacy of blood-based cardioplegic solutions cannot be attributed to a plasma component or to the greater oxygen-carrying capacity of the red blood cell. Future studies should attempt to identify the salutory entity of the red cell responsible for preservation of myocardial oxygen consumption efficiency.

Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline.

OBJECTIVE: A panel was convened by the Health and Science Policy Committee of the American College of Chest Physicians to develop a clinical practice guideline on the medical and surgical treatment of parapneumonic effusions (PPE) using evidence-based methods. OPTIONS AND OUTCOMES CONSIDERED: Based on consensus of clinical opinion, the expert panel developed an annotated table for evaluating the risk for poor outcome in patients with PPE. Estimates of the risk for poor outcome were based on the clinical judgment that, without adequate drainage of the pleural space, the patient with PPE would be likely to have any or all of the following: prolonged hospitalization, prolonged evidence of systemic toxicity, increased morbidity from any drainage procedure, increased risk for residual ventilatory impairment, increased risk for local spread of the inflammatory reaction, and increased mortality. Three variables, pleural space anatomy, pleural fluid bacteriology, and pleural fluid chemistry, were used in this annotated table to categorize patients into four separate risk levels for poor outcome: categories 1 (very low risk), 2 (low risk), 3 (moderate risk), and 4 (high risk). The panel's consensus opinion supported drainage for patients with moderate (category 3) or high (category 4) risk for a poor outcome, but not for patients with very low (category 1) or low (category 2) risk for a poor outcome. The medical literature was reviewed to evaluate the effectiveness of medical and surgical management approaches for patients with PPE at moderate or high risk for poor outcome. The panel grouped PPE management approaches into six categories: no drainage performed, therapeutic thoracentesis, tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery (VATS), and surgery (including thoracotoiny with or without decortication and rib resection). The fibrinolytic approach required tube thoracostomy for administration of drug, and VATS included post-procedure tube thoracostomy. Surgery may have included concomitant lung resection and always included postoperative tube thoracostomy. All management approaches included appropriate treatment of the underlying pneumonia, including systemic antibiotics. Criteria for including articles in the panel review were adequate data provided for >/=20 adult patients with PPE to allow evaluation of at least one relevant outcome (death or need for a second intervention to manage the PPE); reasonable assurance provided that drainage was clinically appropriate (patients receiving drainage were either category 3 or category 4) and drainage procedure was adequately described; and original data were presented. The strength of panel recommendations on management of PPE was based on the following approach: level A, randomized, controlled trials with consistent results or individual randomized, controlled trial with narrow confidence interval (CI); level B, controlled cohort and case control series; level C, historically controlled series and case series; and level D, expert opinion without explicit critical appraisal or based on physiology, bench research, or "first principles." EVIDENCE: The literature review revealed 24 articles eligible for full review by the panel, 19 of which dealt with the primary management approach to PPE and 5 with a rescue approach after a previous approach had failed. Of the 19 involving the primary management approach to PPE, there were 3 randomized, controlled trials, 2 historically controlled series, and 14 case series. The number of patients included in the randomized controlled trials was small; methodologic weaknesses were found in the 19 articles describing the results of primary management approaches to PPE. The proportion and 95% CI of patients suffering each of the two relevant outcomes (death and need for a second intervention to manage the PPE) were calculated for the pooled data for each management approach from the 19 articles on the primary management approach. (ABST