REVIEW URRENT C OPINION
Distinguishing complicated from uncomplicated parapneumonic effusions Jose´ M. Porcel
Purpose of review Treatment of parapneumonic effusions (PPEs) is challenged by the decision of whether or not to insert chest tubes. This review focuses on the factors that may aid in determining which patients require an immediate drainage of the pleural space, that is, have a complicated PPE. Recent findings Clinical guidelines advocate the evaluation of radiological (large effusion or loculation), bacteriological (Gram-positive stain or culture), biochemical (pH < 7.20 or glucose 0.4). In other words, pleural fluid pH and glucose lack sensitivity, so some complicated PPE cases can be overlooked. Moreover, about 10% of patients with PPEs who exhibit pleural acidosis or low glucose levels can be managed solely with antibiotics. When the pleural effusion is loculated, biochemical parameters may vary markedly from one locule to another [18], which may partially explain the limited discriminatory properties of fluid pH, glucose, and LDH. Finally, to be reliable, pH measurements must be done with a blood gas machine no later than 4 h after the extraction [19]. New potential biomarkers In recent years, many potential biomarkers of complicated PPEs have been tested focusing on the complex cascade of events that are related to the inflammatory and immune responses to bacterial infection [20]. These include complement byproducts (SC5b-9 and C3a-desArg), neutrophil-derived enzymes (elastase and myeloperoxidase), proinflammatory (tumor necrosis factor-a, interleukin-8, interleukin-1b, and vascular endothelial growth factor) and anti-inflammatory (interleukin-1ra, tumor necrosis factor sRI) cytokines, acute-phase reactants (CRP, pentraxin-3, and lipopolysaccharide-binding protein), and miscellaneous tests (soluble triggering receptor expressed on myeloid cells-1, matrix metalloproteinases, and the oxidative stress markers 8-isoprostane and copper and zinc-containing superoxide dismutase). Studies on these novel markers are limited by small sample sizes (Table 2) and the lack of further confirmatory findings (with the possible exception of interleukin-8 and CRP). Most importantly, none have been proven to be superior to the more traditional pleural biochemistries that, in addition, are supported by routine practice and are easier and faster to determine. Among the new biomarkers, only CRP is likely to attain practical applicability in the identification of complicated PPEs, as it is inexpensive and widely available. Based on an increase in sample size, our previous study on pleural fluid CRP as being indicative of chest drainage [29] has been updated, as illustrated in Table 1. At a cutoff level of 100 mg/l, CRP exhibited good discriminative properties, with an area under the curve (0.80) overlapping those of LDH, glucose, and pH, thus arguing against the Volume 21 Number 4 July 2015
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Distinguishing complicated from uncomplicated parapneumonic effusions Porcel Table 1. Accuracy of pleural fluid biochemistries for identifying nonpurulent complicated parapneumonic effusionsa
Pleural fluid parameter pH 7.20
No. of uncomplicated PPE/ complicated PPE tested
Sensitivity (%)
Specificity (%)
203/212
61 (54–67)
87 (81–91)
LRþ 4.6 (3.2–6.6)
LR
AUC
0.45 (0.38–0.54)
0.828 (0.771–0.885)
Glucose 60 mg/dl
220/238
55 (48–61)
89 (84–93)
5 (3.4–7.4)
0.51 (0.44–0.59)
0.784 (0.722–0.847)
LDH 3 times the upper limit of normal for serum
218/235
60 (53–66)
78 (73–83)
2.8 (2.1–3.6)
0.52 (0.44–0.61)
0.793 (0.732–0.853)
CRP 100 mg/l
122/139
53 (44–61)
87 (80–92)
4 (2.5–6.5)
0.55 (0.45–0.66)
0.784 (0.723–0.845)
Glucose 60 mg/dl and CRP 100 mg/l
122/139
37 (29–45)
96 (91–98)
9 (3.1–21.7)
0.66 (0.58–0.75)
–
Glucose 60 mg/dl or CRP 100 mg/l
132/190
80 (74–85)
73 (65–80)
3 (2.3–4)
0.27 (0.20–0.37)
–
95% confidence intervals are expressed in parentheses. AUC, area under the curve; CRP, C-reactive protein; LDH, lactate dehydrogenase; LR, likelihood ratio, PPE, parapneumonic effusion. a This is an update to our pleural database [8].
superiority of one parameter over the others. The combination of two tests using ‘or’ or ‘and’ rules increases sensitivity and specificity, respectively, for labeling complicated PPEs. For example, a patient having both a glucose lower than 60 mg/dl and a CRP higher than 100 mg/l in the pleural fluid almost certainly will need a tube thoracostomy (likelihood ratio positive 9). Moreover, in a study of 47 uncomplicated PPEs and 57 complicated PPEs, combining a serum CRP higher than 200 mg/l with either a fluid glucose lower than 60 mg/dl or pH lower than 7.20 using an ‘and’ rule (wherein a chest tube would be inserted if both tests were positive) also accurately predicted patients who were likely to require pleural space drainage (likelihood ratio positive >13) [35 ]. An earlier smaller study, comprising 34 uncomplicated and 20 complicated PPEs, displayed similar findings: a serum CRP higher than 83 mg/l along with a pleural fluid pH lower than 7.20 yielded an likelihood ratio positive of 23.2 and an likelihood ratio negative of 0.21 for the identification of complicated PPEs [30]. &
RADIOLOGICAL CHARACTERISTICS OF COMPLICATED PARAPNEUMONIC EFFUSIONS As in thoracentesis, imaging may influence the management of PPEs. A small effusion is generally categorized into the noncomplicated subset. For instance, in a study of 63 PPE patients, only 3.5 and 9.5% of those having less than 2 and 3 cm in fluid width [as determined by means of computed tomography (CT)], respectively, required chest drainage as compared with 60 and 81% of the patients with a pleural fluid thickness above these
cutoffs [36]. A subsequent study confirmed that just 5% of 95 patients with PPE measuring below 2.5 cm on CT had poor outcomes directly related to the pleural infection [37]. In contrast, an effusion’s size equal to or greater than half the hemithorax on a chest radiograph, which is large enough to produce dyspnea, is an obvious reason to initially drain a nonpurulent PPE, regardless of what their biochemical and microbiological characteristics are. Large free-flowing PPEs (1/2 hemithorax), as well as those characterized by loculations or a thickened parietal pleura, fall into category 3 according to the American College of Chest Physicians classification, which implies an explicit draining recommendation [16]. The role of ultrasonography in uncomplicated– complicated PPE discrimination has not been completely established. Bedside thoracic ultrasound is considered to be a first-line investigative procedure in cases of suspected PPE. It is an excellent method for visualizing locutations, septations, homogenously echogenic effusions, and parietal pleural thickening. All these echographic signs are often indicative of PPEs [38], but by themselves do not necessarily predict drainage requirements. One study found a higher treatment failure rate of small-bore catheters for complex septated effusions compared with nonseptated effusions (49 vs. 20%) [39], yet the clinical implications of this finding are uncertain. A contrast-enhanced CT scan is normally reserved for patients who have failed initial medical management and for whom an evaluation for multiloculated collections or underlying abnormalities, which were not seen on a pleural ultrasound, becomes imperative. Several CT features have been
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349
Diseases of the pleura Table 2. Studies on new pleural fluid tests for labeling nonpurulent complicated parapneumonic effusions No. of patients with uncomplicated/ complicated PPE tested
Test
Sensitivity (%)
Specificity (%)
LRþ
LR
Complement activation products C3a-desArg > 4000 mg/l [21]
12/15
87
67
2.6
0.2
SC5b-9 > 2000 mg/l [21]
12/19
100
75
4
–
Neutrophil markers Neutrophil elastase > 3500 mg/l [22]
59/34
70
84
4.63
0.35
Myeloperoxidase > 3000 mg/l [23]
34/16
87
85
5.95
0.15
Proinflammatory cytokines TNF-a 80 pg/ml [24]
35/23
78
89
6.8
0.25
IL-8 1000 pg/ml [25]
49/51
84
82
4.6
0.19
1937 pg/ml [26]a
26/38
95
100
–
0.05
>1805 pg/ml [27]a
30/30
100
98
50
–
IL-1b > 3.9 pg/ml [28]
26/34
100
71
3.4
–
VEGF > 1975 pg/ml [26]a
26/38
90
100
–
0.1
26/34
100
61
2.5
–
26/34
86
62
2.2
0.23
CRP 100 mg/l [29]
78/92
58
88
5
0.48
>78.5 mg/l [30]a
34/20
84
65
2.4
0.25
LBP 17 mg/ml [31]
60/68
76
81
4
0.30
10/9
67
80
3.3
0.41
a
Anti-inflammatory cytokines IL-1ra > 1252 pg/ml [28]a a
TNF sRI > 9272 pg/ml [28] Acute-phase response proteins
Pentraxin-3 > 31 ng/ml [32] Miscellaneous tests sTREM-1 180 pg/ml [31]
60/68
72
82
3.9
0.34
MMP-2 343 ng/ml [33]
27/17
82
85
5.56
0.21
MMP-8 > 115 ng/ml [33]
86
73
3.2
0.18
MMP-9 > 208 ng/ml [33]
88
74
3.4
0.16
8-Isoprostane > 35.1 pg/ml [34]
31/20
100
58
2.4
–
Cu/Zn SOD > 94 ng/ml [34]
31/20
85
64.5
2.4
0.23
CRP, C-reactive protein; Cu/Zn SOD, copper and zinc-containing superoxide dismutase; IL, interleukin; LBP, lipopolysaccharide-binding protein; LR, likelihood ratio; MMP, matrix metalloproteinases; PPE, parapneumonic effusion; SC5b-9, terminal complement complex; sTREM, soluble triggering receptor expressed on myeloid cells; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor. a Some complicated PPEs could have been purulent (i.e., empyema).
described in complicated PPEs [9,40]: the split pleural sign (i.e., enhancement of the thickened inner visceral and outer parietal pleura, with separation by a collection of pleural fluid), smooth thickening of parietal pleura, increased attenuation of extrapleural fat, loculations, microbubbles, or a combination of these. Nevertheless, whether these CT morphologic characteristics may help formulate management decisions about drainage has not been systematically studied.
CONCLUSION The early identification of patients with nonpurulent PPEs who will eventually require drainage of 350
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the pleural space is still challenging. In clinical practice, when and how to proceed with chest tube placement is left to the discretion of the attending physician. The presence of large or loculated effusions or the aspiration of fluids with a purulent appearance or certain microbiological (positive Gram stains or cultures) or biochemical (low pH or glucose, high CRP) characteristics are powerful indicators of the need for tube thoracostomy in the setting of PPEs. Moreover, the ease and low morbidity of inserting a small-bore chest catheter under ultrasound guidance makes the placement of an unnecessary chest tube a better choice rather than to omit one when it is necessary. Volume 21 Number 4 July 2015
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Distinguishing complicated from uncomplicated parapneumonic effusions Porcel
Acknowledgements The author appreciates the assistance of Dr Silvia Bielsa in the preparation of the article. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Falguera M, Carratala` J, Bielsa S, et al. Predictive factors, microbiology and outcome of patients with parapneumonic effusion. Eur Respir J 2011; 38:1173–1179. 2. Viasus D, Di Yacovo S, Garcia-Vidal C, et al. Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years. Medicine (Baltimore) 2013; 92:51–60. 3. Reissig A, Copetti R, Mathis G, et al. Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study. Chest 2012; 142:965–972. 4. Finch S, Chalmers JD. Parapneumonic effusions: epidemiology and predictors of pleural infection. Curr Respir Care Rep 2014; 3:52–60. 5. Nie W, Liu Y, Ye J, et al. Efficacy of intrapleural instillation of fibrinolytics for treating pleural empyema and parapneumonic effusion: a meta-analysis of randomized control trials. Clin Respir J 2014; 8:281–291. 6. Corrales-Medina VF, Musher DM, Wells GA, et al. Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality. Circulation 2012; 125:773–781. 7. Søgaard M, Nielsen RB, Nørgaard M, et al. Incidence, length of stay, and prognosis of hospitalized patients with pleural empyema: a 15-year Danish nationwide cohort study. Chest 2014; 145:189–192. 8. Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol 2014; 50:161–165. 9. Light RW. Pleural diseases. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. 10. Chung JH, Lee SH, Kim KT, et al. Optimal timing of thoracoscopic drainage and decortication for empyema. Ann Thorac Surg 2014; 97:224–229. 11. Menzies SM, Rahman NM, Wrightson JM, et al. Blood culture bottle culture of pleural fluid in pleural infection. Thorax 2011; 66:658–662. 12. Maskell NA, Batt S, Hedley EL, et al. The bacteriology of pleural infection by genetic and standard methods and its mortality significance. Am J Respir Crit Care Med 2006; 174:817–823. 13. Marks DJ, Fisk MD, Koo CY, et al. Thoracic empyema: a 12-year study from a UK tertiary cardiothoracic referral centre. PLoS One 2012; 7:e30074. 14. Meyer CN, Rosenlund S, Nielsen J, Friis-Møller A. Bacteriological aetiology and antimicrobial treatment of pleural empyema. Scand J Infect Dis 2011; 43:165–169. 15. Insa R, Marı´n M, Martı´n A, et al. Systematic use of universal 16S rRNA gene polymerase chain reaction (PCR) and sequencing for processing pleural effusions improves conventional culture techniques. Medicine (Baltimore) 2012; 91:103–110. 16. Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest 2000; 118:1158–1171.
17. Davies HE, Davies RJ, Davies CW; BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65 (Suppl 2):ii41–53. 18. Maskell NA, Gleeson FV, Darby M, Davies RJ. Diagnostically significant variations in pleural fluid pH in loculated parapneumonic effusions. Chest 2004; 126:2022–2024. 19. Porcel JM. Diagnosis of pleural effusions. Hosp Med Clin 2013; 2:e337– e357. 20. Porcel JM. Pleural fluid tests to identify complicated parapneumonic effusions. Curr Opin Pulm Med 2010; 16:357–361. 21. Vives M, Porcel JM, Ga´zquez I, et al. Pleural SC5b-9: a test for identifying complicated parapneumonic effusions. Respiration 2000; 67:433–438. 22. Alema´n C, Alegre J, Segura RM, et al. Polymorphonuclear elastase in the early diagnosis of complicated pyogenic pleural effusions. Respiration 2003; 70:462–467. 23. Alegre J, Jufresa J, Segura R, et al. Pleural-fluid myeloperoxidase in complicated and noncomplicated parapneumonic pleural effusions. Eur Respir J 2002; 19:320–325. 24. Porcel JM, Vives M, Esquerda A. Tumor necrosis factor-alpha in pleural fluid: a marker of complicated parapneumonic effusions. Chest 2004; 125:160– 164. 25. Porcel JM, Galindo C, Esquerda A, et al. Pleural fluid interleukin-8 and Creactive protein for discriminating complicated nonpurulent from uncomplicated parapneumonic effusions. Respirology 2008; 13:58–62. 26. Chung CL, Hsiao SH, Hsiao G, et al. Clinical importance of angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusions. PLoS One 2013; 8:e53169. 27. Petrusevska Marinkovic S, Kondova Topuzovska I, Milenkovic Z, et al. Role of interleukin-8 in differentiation of uncomplicated from complicated parapneumonic effusion. Prilozi 2011; 32:101–111. 28. Marchi E, Vargas FS, Acencio MM, et al. Proinflammatory and antiinflammatory cytokine levels in complicated and noncomplicated parapneumonic pleural effusions. Chest 2012; 141:183–189. 29. Porcel JM, Bielsa S, Esquerda A, et al. Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions. Eur J Intern Med 2012; 23:447–450. 30. Skouras V, Boultadakis E, Nikoulis D, et al. Prognostic value of C-reactive protein in parapneumonic effusions. Respirology 2012; 17:308–314. 31. Porcel JM, Vives M, Cao G, et al. Biomarkers of infection for the differential diagnosis of pleural effusions. Eur Respir J 2009; 34:1383–1389. 32. Ozsu S, Abul Y, Mentese A, et al. Pentraxin-3: a novel biomarker for discriminating parapneumonic from other exudative effusions. Respirology 2013; 18:657–662. 33. Oikonomidi S, Kostikas K, Kalomenidis I, et al. Matrix metalloproteinase levels in the differentiation of parapneumonic pleural effusions. Respiration 2010; 80:285–291. 34. Tsilioni I, Kostikas K, Kalomenidis I, et al. Diagnostic accuracy of biomarkers of oxidative stress in parapneumonic pleural effusions. Eur J Clin Invest 2011; 41:349–356. 35. Bielsa S, Valencia H, Ruiz-Gonza´lez A, et al. Serum C-reactive protein as an & adjunct for identifying complicated parapneumonic effusions. Lung 2014; 192:577–581. This series of 104 patients with nonpurulent PPEs showed that a serum CRP higher than 200 mg/l, when combined with the classical pleural fluid parameters pH and glucose, improved the identification of those who needed chest drainage. 36. Skouras V, Awdankiewicz A, Light RW. What size parapneumonic effusions should be sampled? Thorax 2010; 65:91. 37. Moffett BK, Panchabhai TS, Anaya E, et al. Computed tomography measurements of parapneumonic effusion indicative of thoracentesis. Eur Respir J 2011; 38:1406–1411. 38. Pinotti KF, Ribeiro SM, Cataneo AJ. Thorax ultrasound in the management of pediatric pneumonias complicated with empyema. Pediatr Surg Int 2006; 22:775–778. 39. Chen CH, Chen W, Chen HJ, et al. Transthoracic ultrasonography in predicting the outcome of small-bore catheter drainage in empyemas or complicated parapneumonic effusions. Ultrasound Med Biol 2009; 35:1468– 1474. 40. Tobin CL, Porcel JM, Wrightson JM, et al. Diagnosis of pleural infection: state of the art. Curr Respir Care Rep 2012; 1:101–110.
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351
Distinguishing complicated from uncomplicated parapneumonic effusions Jose´ M. Porcel
Purpose of review Treatment of parapneumonic effusions (PPEs) is challenged by the decision of whether or not to insert chest tubes. This review focuses on the factors that may aid in determining which patients require an immediate drainage of the pleural space, that is, have a complicated PPE. Recent findings Clinical guidelines advocate the evaluation of radiological (large effusion or loculation), bacteriological (Gram-positive stain or culture), biochemical (pH < 7.20 or glucose 0.4). In other words, pleural fluid pH and glucose lack sensitivity, so some complicated PPE cases can be overlooked. Moreover, about 10% of patients with PPEs who exhibit pleural acidosis or low glucose levels can be managed solely with antibiotics. When the pleural effusion is loculated, biochemical parameters may vary markedly from one locule to another [18], which may partially explain the limited discriminatory properties of fluid pH, glucose, and LDH. Finally, to be reliable, pH measurements must be done with a blood gas machine no later than 4 h after the extraction [19]. New potential biomarkers In recent years, many potential biomarkers of complicated PPEs have been tested focusing on the complex cascade of events that are related to the inflammatory and immune responses to bacterial infection [20]. These include complement byproducts (SC5b-9 and C3a-desArg), neutrophil-derived enzymes (elastase and myeloperoxidase), proinflammatory (tumor necrosis factor-a, interleukin-8, interleukin-1b, and vascular endothelial growth factor) and anti-inflammatory (interleukin-1ra, tumor necrosis factor sRI) cytokines, acute-phase reactants (CRP, pentraxin-3, and lipopolysaccharide-binding protein), and miscellaneous tests (soluble triggering receptor expressed on myeloid cells-1, matrix metalloproteinases, and the oxidative stress markers 8-isoprostane and copper and zinc-containing superoxide dismutase). Studies on these novel markers are limited by small sample sizes (Table 2) and the lack of further confirmatory findings (with the possible exception of interleukin-8 and CRP). Most importantly, none have been proven to be superior to the more traditional pleural biochemistries that, in addition, are supported by routine practice and are easier and faster to determine. Among the new biomarkers, only CRP is likely to attain practical applicability in the identification of complicated PPEs, as it is inexpensive and widely available. Based on an increase in sample size, our previous study on pleural fluid CRP as being indicative of chest drainage [29] has been updated, as illustrated in Table 1. At a cutoff level of 100 mg/l, CRP exhibited good discriminative properties, with an area under the curve (0.80) overlapping those of LDH, glucose, and pH, thus arguing against the Volume 21 Number 4 July 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Distinguishing complicated from uncomplicated parapneumonic effusions Porcel Table 1. Accuracy of pleural fluid biochemistries for identifying nonpurulent complicated parapneumonic effusionsa
Pleural fluid parameter pH 7.20
No. of uncomplicated PPE/ complicated PPE tested
Sensitivity (%)
Specificity (%)
203/212
61 (54–67)
87 (81–91)
LRþ 4.6 (3.2–6.6)
LR
AUC
0.45 (0.38–0.54)
0.828 (0.771–0.885)
Glucose 60 mg/dl
220/238
55 (48–61)
89 (84–93)
5 (3.4–7.4)
0.51 (0.44–0.59)
0.784 (0.722–0.847)
LDH 3 times the upper limit of normal for serum
218/235
60 (53–66)
78 (73–83)
2.8 (2.1–3.6)
0.52 (0.44–0.61)
0.793 (0.732–0.853)
CRP 100 mg/l
122/139
53 (44–61)
87 (80–92)
4 (2.5–6.5)
0.55 (0.45–0.66)
0.784 (0.723–0.845)
Glucose 60 mg/dl and CRP 100 mg/l
122/139
37 (29–45)
96 (91–98)
9 (3.1–21.7)
0.66 (0.58–0.75)
–
Glucose 60 mg/dl or CRP 100 mg/l
132/190
80 (74–85)
73 (65–80)
3 (2.3–4)
0.27 (0.20–0.37)
–
95% confidence intervals are expressed in parentheses. AUC, area under the curve; CRP, C-reactive protein; LDH, lactate dehydrogenase; LR, likelihood ratio, PPE, parapneumonic effusion. a This is an update to our pleural database [8].
superiority of one parameter over the others. The combination of two tests using ‘or’ or ‘and’ rules increases sensitivity and specificity, respectively, for labeling complicated PPEs. For example, a patient having both a glucose lower than 60 mg/dl and a CRP higher than 100 mg/l in the pleural fluid almost certainly will need a tube thoracostomy (likelihood ratio positive 9). Moreover, in a study of 47 uncomplicated PPEs and 57 complicated PPEs, combining a serum CRP higher than 200 mg/l with either a fluid glucose lower than 60 mg/dl or pH lower than 7.20 using an ‘and’ rule (wherein a chest tube would be inserted if both tests were positive) also accurately predicted patients who were likely to require pleural space drainage (likelihood ratio positive >13) [35 ]. An earlier smaller study, comprising 34 uncomplicated and 20 complicated PPEs, displayed similar findings: a serum CRP higher than 83 mg/l along with a pleural fluid pH lower than 7.20 yielded an likelihood ratio positive of 23.2 and an likelihood ratio negative of 0.21 for the identification of complicated PPEs [30]. &
RADIOLOGICAL CHARACTERISTICS OF COMPLICATED PARAPNEUMONIC EFFUSIONS As in thoracentesis, imaging may influence the management of PPEs. A small effusion is generally categorized into the noncomplicated subset. For instance, in a study of 63 PPE patients, only 3.5 and 9.5% of those having less than 2 and 3 cm in fluid width [as determined by means of computed tomography (CT)], respectively, required chest drainage as compared with 60 and 81% of the patients with a pleural fluid thickness above these
cutoffs [36]. A subsequent study confirmed that just 5% of 95 patients with PPE measuring below 2.5 cm on CT had poor outcomes directly related to the pleural infection [37]. In contrast, an effusion’s size equal to or greater than half the hemithorax on a chest radiograph, which is large enough to produce dyspnea, is an obvious reason to initially drain a nonpurulent PPE, regardless of what their biochemical and microbiological characteristics are. Large free-flowing PPEs (1/2 hemithorax), as well as those characterized by loculations or a thickened parietal pleura, fall into category 3 according to the American College of Chest Physicians classification, which implies an explicit draining recommendation [16]. The role of ultrasonography in uncomplicated– complicated PPE discrimination has not been completely established. Bedside thoracic ultrasound is considered to be a first-line investigative procedure in cases of suspected PPE. It is an excellent method for visualizing locutations, septations, homogenously echogenic effusions, and parietal pleural thickening. All these echographic signs are often indicative of PPEs [38], but by themselves do not necessarily predict drainage requirements. One study found a higher treatment failure rate of small-bore catheters for complex septated effusions compared with nonseptated effusions (49 vs. 20%) [39], yet the clinical implications of this finding are uncertain. A contrast-enhanced CT scan is normally reserved for patients who have failed initial medical management and for whom an evaluation for multiloculated collections or underlying abnormalities, which were not seen on a pleural ultrasound, becomes imperative. Several CT features have been
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349
Diseases of the pleura Table 2. Studies on new pleural fluid tests for labeling nonpurulent complicated parapneumonic effusions No. of patients with uncomplicated/ complicated PPE tested
Test
Sensitivity (%)
Specificity (%)
LRþ
LR
Complement activation products C3a-desArg > 4000 mg/l [21]
12/15
87
67
2.6
0.2
SC5b-9 > 2000 mg/l [21]
12/19
100
75
4
–
Neutrophil markers Neutrophil elastase > 3500 mg/l [22]
59/34
70
84
4.63
0.35
Myeloperoxidase > 3000 mg/l [23]
34/16
87
85
5.95
0.15
Proinflammatory cytokines TNF-a 80 pg/ml [24]
35/23
78
89
6.8
0.25
IL-8 1000 pg/ml [25]
49/51
84
82
4.6
0.19
1937 pg/ml [26]a
26/38
95
100
–
0.05
>1805 pg/ml [27]a
30/30
100
98
50
–
IL-1b > 3.9 pg/ml [28]
26/34
100
71
3.4
–
VEGF > 1975 pg/ml [26]a
26/38
90
100
–
0.1
26/34
100
61
2.5
–
26/34
86
62
2.2
0.23
CRP 100 mg/l [29]
78/92
58
88
5
0.48
>78.5 mg/l [30]a
34/20
84
65
2.4
0.25
LBP 17 mg/ml [31]
60/68
76
81
4
0.30
10/9
67
80
3.3
0.41
a
Anti-inflammatory cytokines IL-1ra > 1252 pg/ml [28]a a
TNF sRI > 9272 pg/ml [28] Acute-phase response proteins
Pentraxin-3 > 31 ng/ml [32] Miscellaneous tests sTREM-1 180 pg/ml [31]
60/68
72
82
3.9
0.34
MMP-2 343 ng/ml [33]
27/17
82
85
5.56
0.21
MMP-8 > 115 ng/ml [33]
86
73
3.2
0.18
MMP-9 > 208 ng/ml [33]
88
74
3.4
0.16
8-Isoprostane > 35.1 pg/ml [34]
31/20
100
58
2.4
–
Cu/Zn SOD > 94 ng/ml [34]
31/20
85
64.5
2.4
0.23
CRP, C-reactive protein; Cu/Zn SOD, copper and zinc-containing superoxide dismutase; IL, interleukin; LBP, lipopolysaccharide-binding protein; LR, likelihood ratio; MMP, matrix metalloproteinases; PPE, parapneumonic effusion; SC5b-9, terminal complement complex; sTREM, soluble triggering receptor expressed on myeloid cells; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor. a Some complicated PPEs could have been purulent (i.e., empyema).
described in complicated PPEs [9,40]: the split pleural sign (i.e., enhancement of the thickened inner visceral and outer parietal pleura, with separation by a collection of pleural fluid), smooth thickening of parietal pleura, increased attenuation of extrapleural fat, loculations, microbubbles, or a combination of these. Nevertheless, whether these CT morphologic characteristics may help formulate management decisions about drainage has not been systematically studied.
CONCLUSION The early identification of patients with nonpurulent PPEs who will eventually require drainage of 350
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the pleural space is still challenging. In clinical practice, when and how to proceed with chest tube placement is left to the discretion of the attending physician. The presence of large or loculated effusions or the aspiration of fluids with a purulent appearance or certain microbiological (positive Gram stains or cultures) or biochemical (low pH or glucose, high CRP) characteristics are powerful indicators of the need for tube thoracostomy in the setting of PPEs. Moreover, the ease and low morbidity of inserting a small-bore chest catheter under ultrasound guidance makes the placement of an unnecessary chest tube a better choice rather than to omit one when it is necessary. Volume 21 Number 4 July 2015
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Distinguishing complicated from uncomplicated parapneumonic effusions Porcel
Acknowledgements The author appreciates the assistance of Dr Silvia Bielsa in the preparation of the article. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
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