American Journal of Respiratory and Critical Care Medicine

In pleural infection, medical treatment failure (chest-tube drainage and antibiotics) requires surgery and increases mortality. It would be helpful to predict which patients will fail this approach. We examined clinical predictors in 85 consecutive patients with pleural infection receiving chest drainage and intrapleural fibrinolytics, and recorded age, length of history, antibiotic delay and choice, time to drainage, blood/pleural fluid (PF) bacteriology, PF pH, lactate dehydrogenase (LDH), glucose and appearance, effusion size, pleural thickness on computed tomographic (CT) scan, and survival from time of drainage. Failures (surgery/death) were compared with successes. There were 13 (15%) medical failures. PF purulence was more frequent in medical failures (10 of 13 versus 29 of 72 successes, p < 0.02 chi-square). Absence of purulence was a useful predictor of success (positive predictive value [PPV] 93%). Purulence was not useful in predicting medical failure (PPV 26%). There was a trend for positive blood culture to predict failure (5 of 13 failures versus 11 of 72 successes, p = 0.05 chi-square), but no significant differences in other endpoints. Twelve (14%) patients died in follow-up, all with comorbidity within 400 d after drainage. Probability of survival at 4 yr was 86%. Of endpoints considered in this study, PF purulence was the only useful predictor of outcome with medical therapy in pleural infection. There is good long-term survival from pleural infection. Davies CWH, Kearney SE, Gleeson FV, Davies RJO. Predictors of outcome and long-term survival in patients with pleural infection.

Pleural effusion may develop in up to 44% of patients with community-acquired pneumonia (1). In approximately 10% of these patients a complicated parapneumonic collection or frank pleural empyema develops. This group with pleural infection need effective medical treatment in the first instance to resolve their symptoms, and failure of medical treatment results in the need for surgery and/or death. The frequency with which these patients need surgery ranges from 15% (2) to 68% (3) and mortality can be as high as 58% in people with frank empyema and major comorbid disease (4).

The development of pleural infection is a progressive process during which a free-flowing exudative parapneumonic effusion is transformed into a multiloculated purulent empyema (5). Management involves the use of systemic antibiotics and pleural fluid drainage and is usually managed by medical chest tube drainage or by surgery. Early drainage is desirable to avoid a poor outcome, but drainage itself is associated with a financial cost and some morbidity. It is therefore undesirable to drain an effusion that will remit with antibiotics alone. It would be beneficial in terms of cost and morbidity to be able to predict the potential failure of medical therapy at the time of presentation to hospital, to enable prompt referral of patients who will require surgical drainage.

There have been no studies that have looked at the history, examination, pleural fluid (PF), and radiological characteristics at presentation in patients with pleural infection receiving consistent and aggressive medical management. A number of retrospective studies have tried to assess predictors of outcome by seeking reasons for delay in surgical referral (3, 6-10), which may include misdiagnosis (6), inadequate antibiotics (6), trials of treatment before referral (9), lack of consensus regarding the PF profiles that warrant drainage (7), and delays in acceptance of failure of medical drainage (10). However, these studies have not always included patients unsuitable for surgical referral and confirm the wide variation in management by physicians before referral for surgery (7, 11, 12). We therefore report the clinical predictors of outcome in a prospective, consecutive series of patients with parapneumonic pleural effusion, all receiving consistent, aggressive therapy with antibiotics, radiologically guided chest catheter drainage, and intrapleural fibrinolytics for management of their pleural infection.


Consecutive patients receiving chest tube drainage for possible pleural infection referred to one center between May 1994 and March 1998 were studied. The indication for pleural drainage was the managing physician's clinical judgment. Criteria contributing to this decision included purulent PF, gram stain and/or culture-positive PF, PF acidosis (pH < 7.2), lactate dehydrogenase (LDH) greater than 1,000 IU/L (Light's criteria) (13), and the presence of loculations/septations on radiological imaging in association with persistent systemic sepsis. All patients were identified prospectively and the following indices were recorded: age, length of history prior to admission, delay in initiating antibiotic treatment (defined as not receiving antibiotics until more than 4 d after first seeking medical advice for the current illness), antibiotic choice, time to drainage of the effusion after first recognition on chest radiograph, blood and PF bacteriology, PF pH, LDH, glucose and PF appearance (purulent/nonpurulent). Purulent fluid was defined by the macroscopic appearance of the PF, as fluid with an opaque or cloudy appearance, in the context of clinical pneumonia or a systemic sepsis syndrome.

The chest radiograph at admission to the unit was examined and consensus scored by two radiologists (S.E.K. and F.V.G.) and the PF opacity estimated to the nearest 10% of the affected hemithorax on the chest radiograph. Wherever possible, computed tomographic (CT) scanning was performed at presentation and chest catheter insertion. In these subjects the pleural thickness was measured at the medial, lateral, and posterior site of the maximal effusion, and the maximal pleural thickness recorded.


All patients were managed on a similar protocol. A diagnostic thoracocentesis was obtained and PF characteristics were evaluated as previously described. When “blind” diagnostic aspiration failed to obtain fluid, patients were referred to radiology for ultrasound (US)-guided needle aspiration.

All patients received antibiotic therapy. If cultures were negative, this consisted of intravenous cefuroxime and oral metronidazole for at least 5 d followed by amoxicillin and clavulinic acid until discharge and/or 1 mo. The exact duration of antibiotics depended on the individual patient clinical response. Where cultures were positive, the antibiotics given were those appropriate for the organism.

All patients included in this series received a chest catheter. Drains were all inserted under radiological control, with either US or CT scan guidance. A 14-French catheter was inserted into the most dependent area of the effusion or into the largest locule and connected to underwater seal. All catheters were flushed four hourly with saline and kept on −20 cm H2O suction. Some patients were referred from other physicians within the hospital for management of their pleural infection. In all patients any delay in insertion of drain was recorded, as the number of days until drain insertion after recognition of pleural infection clinically and/or radiologically.

The day after catheter insertion, patients received intrapleural streptokinase (SK) to aid pleural drainage. SK (Streptase; Hoechst UK Limited) 250,000 international units (IU) was dissolved in 30 ml 0.9% saline and retained in the pleural space for 2 h after each administration. At the beginning of the study, SK was administered once daily, but from September 1996, was given 12 hourly for a maximum of 3 d to a maximal cumulative dose of 1.5 million IU. Urokinase (UK) 100,000 IU daily was reserved for patients with known previous exposure to SK or who developed an allergic reaction from SK during current treatment.

Failure of medical treatment was determined by the presence of persistent sepsis syndrome (fever and/or persistent leukocytosis and/ or elevated C-reactive protein) in association with a residual pleural collection confirmed radiologically. These patients were referred for surgery within 7 d of drain insertion if this was considered appropriate with the patients' clinical situation. The choice of surgical procedure was left to the discretion of the relevant surgeon and decisions about surgical referral were made before any data analysis.

In those patients who responded to medical treatment, chest catheters were removed when drainage fell to below 150 ml daily (including returned flushes) for 2 consecutive days. After discharge all patients were followed as outpatients for a minimum of 3 mo to monitor the resolution of symptoms and radiology. Long-term survival was documented by examining a combination of hospital records and by direct contact with the patients' primary care physician. The cause of death was clarified by examination of entries on the death certificate, provided by the Office for National Statistics, Southport, England.


For the analysis, failure of medical therapy was defined as the requirement for surgery and/or death. The clinical features at presentation were compared in those where medical therapy failed with those where it succeeded. Statistical analysis was performed using the SPSS statistical software package (SPSS Software; SPSS Inc., Chicago, IL). Wilcoxon's rank sum test was used unless otherwise stated and a decision matrix used to calculate predictive values. Kaplan-Meier survival curves were used to assess probability of survival.


Eighty-five patients with parapneumonic pleural effusions receiving drainage and intrapleural fibrinolytics were studied. The clinical characteristics of the subjects are described in Table 1.


Subject Characteristics
Sex, male/female85 (55/30)
Median age, yr (100% range)59 (18–93)
Median length of history prior to admission, d (100% range/25–75% range)11 (2–100/5–24)
Median time to drainage, d (100% range/25–75% range)1 (0–90/0–3)
Median pleural effusion size at presentation on chest  radiograph, to nearest 10% (100% range/25–75% range)40 (20–80/30–60)
PF analysis
 pH median (100% range/25–75% range)7.02 (6.0–7.6/6.81–7.28)
 Glucose median, mmol/L (100% range/25–75% range)1.0 (0.1–8.3/0.5–4.0)
 LDH median, IU/L (100% range/25–75% range)2,679 (192–46,728/835–4,620)
Purulent/nonpurulent (n = 84)39/45
Streptococcus pneumoniae 12
Staphylococcus aureus  4
Enterococcus  2
Streptococcus milleri  2
Escherichia coli  1
 Gram/culture negative64
Blood cultures positive16
SK, median number doses (100% range)4.0 (1-6)
Total hospital stay median, d (100% range/25–75% range)15 (6–140/11–24)
Hospital stay post-drain insertion median, d (100% range/25–75% range)14 (4–131/9–20)

There were 13 (15%) failures of medical therapy with 11 (13%) patients requiring surgery. All 11 patients receiving surgery underwent a thoracotomy and decortication. There were four in-hospital deaths in total (4.7%) including two after surgery.

In the majority of patients, the pleural collection had developed in association with community-acquired pneumonia. There were alternative likely causes in a number of patients including aspiration pneumonia (n = 3), endobronchial carcinoma with distal pneumonia (n = 1), and postoperative pneumonia (n = 4). Comorbidity included chronic obstructive airways disease (n = 2), malignancy (n = 7), chronic renal failure (n = 3), neurological disease (n = 4), ankylosing spondylitis (n = 2), diabetes (n = 2), and immunosuppression following renal transplantation (n = 3), Crohn's disease (n = 1), and Wegener's granulomatosis (n = 1). A delay in the administration of antibiotics before admission to the unit was observed in 33 patients including five (38%) failing medical treatment and 28 (39%) medical successes. Overall, there was wide variation in the length of illness before presentation to hospital (median 11 d, range 2 to 100 d) and subsequent total stay in hospital (median stay 15 d, range 6 to 140 d) and hospital stay after chest drain insertion (median stay 14 d, range 4 to 131 d).

Complications of Medical Therapy

None of the patients had any complications from radiological insertion of the chest catheter. One patient had received an unsuccessful large-bore chest drain/thoracostomy prior to referral which had been removed before admission to the unit. All patients received at least 1 dose of SK (mean 4.03 doses, range 1 to 6 doses) and three patients received UK after febrile reactions thought secondary to SK. There were no hemorrhagic complications from intrapleural fibrinolytic therapy.


The PF opacity at presentation on the chest radiograph was assessed in 73 patients. Of those excluded, one patient had only consolidation at presentation but developed a subsequent effusion and frank empyema, five patients had pyopneumothorax making opacity size difficult to estimate, and the X-ray films for six patients were untraceable. A subgroup of 46 (54%) patients had CT scan performed at the time of drain insertion which included 10 of the patients finally requiring surgery.

Comparison between Medical Success and Failure

Table 2 shows the clinical characteristics of the two patient groups divided by successful or failed medical treatment. Frank pleural fluid purulence was more frequent in patients failing medical therapy (10 of 13 [77%] failures versus 29 of 72 [40%] successes; p < 0.02 chi-square) and the absence of purulence was a useful predictor of medical success (positive predictive value [PPV] 93%; negative predictive value [NPV] 26%; sensitivity 59%; specificity 77%; accuracy 62%). The presence of frank purulence was not clinically useful in predicting failure of medical treatment (PPV 26%, NPV 93%, sensitivity 77%, specificity 59%, accuracy 62%). There was a trend toward positive blood culture predicting medical failure (5 of 13 failures versus 11 of 72 successes, p = 0.05 chi-square). There were no clinically or statistically significant differences in any other endpoint. In particular there were no differences in symptom duration before admission, PF biochemistry (Figure 1), or positive culture, age, delayed chest drainage, delay to antibiotic administration, pleural collection size at presentation, or CT-assessed maximal pleural thickness at the time of drain insertion (Figure 2).


Medical Failures (n = 13)Medical Successes (n = 72)p Value
Length of history prior to admission  (median/25–75th percentile), d14/4–2410/5–23NS
Time to drainage (median/25–75th percentile), d2/1–41/0–3NS
Pleural effusion size at presentation on chest radiograph, to  nearest 10% (median/25–75th percentile)40/35–7040/30–60NS
PF analysis
 pH (median/25–75th percentile)7.04/6.7–7.257.02/6.82–7.28NS
 Glucose (median/25–75th percentile), mmol/L1.1/0.45–4.41.1/0.5–3.9NS
 LDH (median/25–75th percentile), IU/L3,654/418–46,7282,167/875–4,284NS
 Purulent10 (77%)29 (40%)< 0.02
 Nonpurulent 3 (23%)42 (58%)NS
 PF culture positive 5 (38%)15 (21%)NS
Blood cultures positive 5 (38%)11 (15%)NS
Maximal pleural thickness on CT scan  (mean ± SD), mm (n = 46)3.25/2.65–3.853.10/2.55–3.45NS
Deaths 2 (15%)2 (3%)NS

There was an increase in the total duration of hospital stay (p = 0.01) and the duration of hospital stay after drain insertion (p = 0.01) in patients with negative PF microbiological culture. There were no clinically or statistically significant differences in the total or post–drain insertion duration of hospital stay with any of the other variables.

Long-term Survival

Survival details were expressed as survival post–drain insertion. A total of 12 patients (14%) died during the follow-up period including the in-hospital deaths. All deaths occurred within the first 400 d after drain insertion (Figure 3), and none of the deaths were directly attributed to sepsis. All patients who died after discharge had significant comorbidity (Table 3). There was no statistical difference between long-term survival in those with purulent versus nonpurulent pleural effusions. The probability of survival at 4 yr after drain insertion for pleural infection is 86%.


Cause of Death
Ischemic heart disease4
 Breast carcinoma1
 Cervical carcinoma1
 Squamous carcinoma bronchus1

This study reports the results of clinical, PF, and radiological characteristics as predictors of outcome with medical therapy in 85 consecutive patients with pleural infection. This is the first series describing a prospectively identified cohort of consecutive patients with pleural infection requiring chest drainage, who have all received similar investigation and management in one center. All patients were aggressively and consistently managed by antibiotics, radiologically guided chest catheter drainage, and intrapleural fibrinolytics. Of the endpoints considered in this study, the absence of frank PF purulence was the only clinically useful predictor of successful outcome with medical therapy. However, the presence of purulent PF did not predict the failure of medical treatment and the need for surgery and/or death. Negative PF microbiological culture was associated with increased hospital stay, but none of the other endpoints was associated with length of hospital stay. There is good long-term survival from pleural infection in this series of patients.

The management strategy was designed to be aggressive and “optimal.” Radiological placement of small-bore catheters was chosen as this has been used successfully both as primary drainage and as a successful salvage technique when larger drains are blocked or fail to resolve pleural infection (14-18). Similarly, there are observational data (19) and two small randomized controlled trials (20, 21) to suggest intrapleural fibrinolytics may be a useful adjunct to aid PF drainage. Both these strategies were therefore included in this management protocol, enabling a reliable comparison between the clinical characteristics of those succeeding and those failing aggressive medical treatment. It should be noted that the efficacy of intrapleural SK is still controversial and is currently being properly assessed in a large U.K. Medical Research Council/British Thoracic Society sponsored multicenter study.

There are currently no clear data to define the point at which a patient with empyema should proceed to surgical intervention. Patients should be considered for surgery if they have a residual sepsis syndrome in association with a persistent pleural collection, despite aggressive medical management. The use of video-assisted thoracoscopic surgery (VATS) to drain an infected pleural space has been a major recent innovation in the management of pleural empyema. VATS intervention is reducing the frequency with which open surgery is needed (22) and may encourage earlier surgical intervention in the fibrinopurulent phase (22-24). The exact role of VATS in the management of empyema is currently unclear, and there is only one small controlled study directly comparing surgical versus medical therapy. Wait and coworkers (25) studied 20 patients with pleural infection, who were suitable for general anesthesia, and randomized them to receive immediate VATS or intrapleural streptokinase (IPSK) for 3 d. Chest drains were not inserted under radiological guidance in the medical group. The surgical group had higher primary treatment success and all SK medical failures were salvaged by VATS, without requiring thoracotomy. VATS was not widely available for this patient group when we began this prospective study; consequently none of the patients was referred or received VATS procedures.

None of the clinical or pleural fluid characteristics studied could reliably predict the need for surgery or death. Surprisingly, delay in the administration of antibiotics before admission to hospital and the time to drainage from recognition of pleural effusion, did not affect the failure rate of medical therapy. Previous studies have suggested that delay to drainage of an infected pleural space is associated with increased morbidity and hospital stay (3, 6-9). This may be related to sampling bias in the various series. Three of the previous reports are from surgical centers and so report a selected group of patients (3, 6, 9), and the others are not a prospective, unselected series (7, 8).

Another recent study has also tried to identify predicting factors for outcome of tube thoracostomy in patients with complicated parapneumonic effusion or empyema (26). This study is not directly comparable with ours because it reports a selected series of patients managed in other centers before referral. This case selection is emphasized by some patients receiving thoracotomy and decortication as a “first-line” procedure, the most frequent organism isolated from pleural fluid being Klebsiella pneumoniae, usually an infrequent pathogen. Not all patients received radiological drain placement and fibrinolytics were only used in 18 of 121 subjects, with only 50% success. In contrast, our study includes only patients managed in a similar and aggressive manner, and consists predominantly of patients with community-acquired infection. It is therefore likely to be more generalizable in its conclusions.

In the same series by Huang and coworkers (26), failure of tube thoracostomy was associated with the presence of loculations, larger effusions, and a low PF white cell count. The finding of a low leukocyte count was surprising to the authors of the study, and seems counterintuitive. This observation is also inconsistent with the results of our study. We found that macroscopically purulent PF (indicating many white cells) was associated with a poorer outcome. We hypothesize that the differing results may be related to the case selection in the Taiwan series.

PF pH predicts the likelihood of spontaneous resolution of parapneumonic effusion and when PF pH is below 7.2 it is unusual for effusions to resolve without formal drainage (13, 27– 30). Consistent with the established evidence (13, 29), we use PF pH as a bedside test to identify patients requiring pleural drainage, but these results suggest this index is not also helpful at predicting which patients will go on to fail medical treatment after drainage. This is consistent with the pathophysiology of pleural infection where the invasion of bacteria into the pleural space is associated with the development of PF acidosis, but it is primarily the reduction in fibrinolytic activity with associated fibrin deposition and consequent fibroblast activation that will reduce the likelihood of successful PF drainage and therefore predict the success or failure of medical therapy (5).

In our series, some patients without frank purulence or acidosis demonstrated loculation of their effusion and a sepsis syndrome, and therefore had pleural drainage and fibrinolytics. This included two patients with an initial pleural pH > 7.2 who failed to resolve their sepsis syndrome and required surgical debridement despite aggressive medical management. These occasional cases confirm that although pleural pH is specific in predicting the need for pleural drainage (13), it is less than 100% sensitive; an observation consistent with that of Poe and coworkers (31), who found that PF analysis including pH did not accurately predict eventual surgery in a selected series of patients. Clinicians should be aware of this occasional trap.

Delay to antibiotic administration is thought to be of significance in the development of pleural infection (5, 32), and in this series there was a high incidence of antibiotic delay which we have defined as greater than 4 d from seeking medical advice for the current illness. Despite a delay in receiving antibiotics prior to admission in 39% patients, the difference in antibiotic use was not associated with a varying outcome in this series. There was no association with the type of antibiotic given by the general practitioner and patient outcome.

There was an increase in the total duration of hospital stay and stay after drain insertion, in patients with negative PF microbiological culture. This is difficult to explain, but may represent the presence of anaerobic bacteria not identified by our laboratory. A previous series has suggested that pleural infection caused by nonpneumococcal organisms, including anaerobes, is associated with a longer clinical recovery (30). There were, however, no clinically or statistically significant differences in the total or post–drain insertion duration of hospital stay with any of the other variables.

Our series does not support the radiological findings of the British Thoracic Society (BTS) study of empyema, where larger pleural collections (> 40% of the hemithorax) were more likely to require surgery (11). Theoretically, pleural collection size should not be the main determinant of the need for surgery—it is the failure of adequate drainage rather than initial size of pleural collection that will lead to the failure of treatment. Inadequate drainage may result from a number of possible factors including poor drain placement, viscous pus, and/or loculations and drain blockage. It is possible that our use of radiological catheters and fibrinolytics (neither widely used in the BTS series) minimized the effects of these factors and hence reduced the effect of pleural collection size.

A subgroup of 46 patients had CT scanning as part of initial assessment for placement of drainage catheter. Pleural thickening in patients with parapneumonic exudates is usually smooth with enhancement of the parietal pleura and extrapleural tissues (33-35). It has been suggested that pleural thickness is greater in patients subsequently requiring decortication for empyema (34), but this is not confirmed by our series. We found the thickness of the pleura in the group failing medical treatment was no different from that in those treated successfully, and some of those responding to medical treatment had substantially thicker pleural peels than some requiring surgery (Figure 2). Thus, pleural thickness on CT scan does not predict outcome either, with pleural peels resolving over several weeks in patients spared surgery (36). Our data do not, therefore support the common opinion that a thick pleural peel makes surgical intervention mandatory.

Perhaps the most interesting feature of this report is the low in-hospital mortality rate (4.7%), compared with some other reported series (2, 4, 9, 11, 37, 38). This shows that early and aggressive medical management for patients with pleural infection is associated with a good outcome and emphasizes the need for rapid and effective intervention in this disease. As well as aggressive medical therapy, this proactive approach should also include an early recognition of failing medical therapy and prompt radiological imaging and surgical involvement.

This is the first study reporting the long-term prognosis in a cohort of consecutive patients with pleural infection. Late mortalities (occurring after hospital discharge) all occurred in the first 400 d after drain insertion and in patients with serious comorbid conditions such as malignancy and ischemic heart disease. The postdischarge prognosis in patients without comorbidity was excellent, with no deaths in this group after discharge.

In conclusion, this study shows that an aggressive medical strategy is associated with a low failure rate in in-hospital medical therapy. It also shows that there are no reliable clinical, PF, or radiological characteristics that will predict failure of medical therapy at the time the patient is first admitted. In particular, outcome was unrelated to pleural thickness on CT scan. The absence of frank pleural purulence does predict a high success rate with medical therapy, but in this series three of 11 (27%) patients requiring surgical drainage had nonpurulent fluid. The long-term survival in these patients is 86% at 4 yr with all late deaths being related to comorbidity and not the primary pleural infection.

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