대한내과학회지 : 제 81 권제 2 호 2011 특집 (Special Review) - Pleural effusion Complicated Pleural Effusion 의진단과치료 가톨릭대학교의과대학호흡기내과 김석찬 Diagnosis and Treatment of Complicated Pleural Effusion Seok Chan Kim Department of Pulmonology, The Catholic University of Korea School of Medicine, Seoul, Korea Parapneumonic effusion is pleural effusion that arises in the pleural space, complicated with bacterial pneumonia. This occurs in at least forty percent of bacterial pneumonia. The usual parapneumonic effusion resolves well with antibiotic therapy. However, if bacteria invade the pleural space, a complicated parapneumonic effusion or empyema may result. In addition to appropriate antibiotic therapy, some parapneumonic effusions and empyemas need additional treatment, such as drainage procedures. The necessity of drainage for treatment of parapneumonic effusions depends on the several types or stages of parapneumonic effusion. Empyemas may need additional intervention beyond simple chest tube drainage, including placement of additional drainage tubes under fluoroscopy, video-assisted thoracoscopy with lysis of adhesions, and decortication. Patients with persistent air leaks often require surgical or endoscopic repair procedures. (Korean J Med 2011;81:143-149) Keywords: Parapneumonic effusion; Empyema 서론부폐렴성늑막삼출액은세균성폐렴이발생한폐에근접한늑막에발생하는늑막삼출액으로서세균성폐렴의 40% 에서도발생한다고알려져있다 [1]. 일반적인부폐렴성늑막삼출액은소량이며적절한항생제치료에잘반응한다. 그러나세균이늑막강까지감염시키는경우에는 complicated parapneumonic effusion 또는농흉 (empyema) 이발생한다. 이런경우에는항생제치료외에도다른부가적인치료를요하게 된다. 본론 Complicated pleural effusion의진단임상양상 Parapneumonic effusion 또는 empyema의임상양상은환자가어떤단계에서내원하였는지와환자의면역상태에따라달리나타나며, 원인균에따라서도달라질수있다. 폐렴의초기단계에서발견되는경우에는별다른합병증없이진단 Correspondence to Seok Chan Kim, M.D., Ph.D. Department of Pulmonology, Seoul St. Mary s Hospital, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-040, Korea Tel: +82-2-2258-6062, Fax: +82-2-599-3589, E-mail: cmcksc@catholic.ac.kr - 143 -
- The Korean Journal of Medicine: Vol. 81, No. 2, 2011 - 되지만, 제대로치료되지못한폐렴으로인하여흉막강내에세균이감염되면농흉으로처음부터진단될수있다. 상당기간동안천천히반복적으로진행된흡인성폐렴으로독성이강하지않은혐기성세균에의한폐렴이진행되는경우에는농흉으로진행된상태로진단되는경우가많다. 그러나심한면역기능장애또는면역억제상태에서는폐렴의초기단계부터농흉으로빠르게진행될수도있다. 흔한임상양상은기침, 발열, 흉막통, 호흡곤란, 객담등이며, 초기증상이나발열, 흉막통의기간등은폐렴과부폐렴흉막삼출액또는농흉을구별하는데결정적인도움을주지는못하는경우가많지만, 단순폐렴보다는합병증이동반된부폐렴흉막삼출액이나농흉에서증상이심하고, 증상지속시간이긴경우가많다. 흉부진찰에서폐렴에서나타나는수포음, 염소울음소리 (egophony), 흉막진동감 (pleural fremitus) 증가등의소견이아닌감소된호흡음및감소된흉막진동감, 둔탁한타진음등이진단에도움이될수있으나상기소견들이불명확한경우가있으므로방사선학적검사가중요하다. 영상의학검사흉부 X-선촬영과초음파검사가진단과치료에중요한역할을한다 [2]. 단순흉부PA 및측면촬영소견에서흉막삼출액의양이 75 ml 이상일경우에 posterior costophrenic sulcus 가소실되며, 175 ml 이상이고인경우에 lateral costophrenic sulcus가소실된다. 500 ml 이상인경우에 diaphragmatic contour 가소실되며, 4번늑골까지흉수가차있는경우에는 1,000 ml 정도에해당한다. 측와위촬영소견에서는 10 ml 이하의흉막액도진단이가능하며, 측와위촬영소견에서소량의늑막액은 1.5 cm 이하의두께, 중등도는 1.5-4.5 cm 두께로보이고, 대량의흉막액은 4.5 cm 이상의두께로보인다 [3]. 와위 (supine) 흉부 X-선사진에서는 175 ml 이상의흉막액이있어야진단이가능하며, 흉막액이고여있는폐측이반대쪽폐에비해뿌옇게보이며, 환자의상체를거상하여촬영하면사라지는경우에의심할수있다 [4]. 흉부단순촬영에서 complicated parapneumonic effusion 또는 empyema가의심되는소견은늑막에있는음영으로서전형적인흉막삼출액과다른윤곽을보이고측와위촬영소견에서흐르지않고고정되어있는경우로서, 이런소견이보이면초음파검사또는 CT 등의추가검사가필요하다. 초음파검사를통하여쉽게 소방성흉막액을확인할수있으며, 종괴와의감별이가능하다. 또한흉막액의양이적거나소방을형성한경우흉수천자를시행할부위를정하는데도움이된다. 일반적으로 empyema 나소방성흉막액의진단에는흉부CT가필요하며, 좀더많은정보를얻기위해서는조영제투여촬영이좀더도움이된다. 벽측흉막의비후시에는농흉이의심되며, 작은공기주머니음영들이흉막삼출액부위에포함되어있어소방성흉막액이의심되는경우에는흉관배액 (chest tube drainage) 또는경피도관배액 (percutaneous catheter drainage) 등의치료에도잘반응하지않을것으로예상할수있다. 추가적으로폐실질의병변이나기도의병변들도진단될수있는장점이있다 [5-7]. 흉수천자 (thoracentesis) 흉수천자는기본적인진단검사로서흉수의성상을확인하고배양검사및항생제감수성검사를시행하기위하여반드시필요하다. 부폐렴흉막삼출액에서흉수천자가필요한일반적인경우는다음과같다 [8]. 첫째, 측와위촬영소견상 10 mm 이상의흉수가보일때둘째, 흉수가 loculation 되어있을때셋째, contrast enhanced CT 에서벽측흉막의비후가관찰되어농흉이의심될때넷째, 초음파소견에서흉막액이확인된경우등이있다. 초음파로흉막천자부위를정하는것이일반적으로도움이되며, loculation이되어있는경우에는초음파나 CT를이용하는것이보다안전하고효과적으로흉수천자를시행할수있다. 흉막액분석흉수천자로얻은흉막액을이용한여러검사가 complicated pleural effusion 및농흉의진단에도움이된다. 미생물검사, 세포진검사, 생화학적검사및 ph검사등이반드시의뢰되어야하며, 흉막액의 ph는 blood gas analyzer를이용하여검사하여야하지만불가능한경우에는흉막액의 glucose 농도측정으로대치하여사용할수도있다 [9]. 일반적으로흉막액의 ph < 7.20 또는 glucose < 60 mg/dl 일경우에는자연적인소실을기대하기어려우므로배액이필요하지만이기준은임상적으로확실히증명된것은아니므로너무이기준을엄격하게적용하는것은권장되지는않는다 [9]. American College of Chest Physicians (ACCP) consensus guideline에서는 ph < 7.20인경우에배액술을권장하고있다 [8]. 그러나 - 144 -
- Seok Chan Kim. Diagnosis and treatment of complicated pleural effusion - 이런경우에는 pleural fluid acidosis 나 low glucose 수치를나타낼수있는악성종양, 결핵, 류마티스성늑막염또는 lupus 늑막염등을감별하여야한다 [10]. 감염성질환의 biomarker들인 C-reactive protein (CRP), procalcitonin, STREM-1 등이농흉의진단에도움이되는지를확인하는연구들이있었지만기존의생화학검사들에비해우월한유용성이증명되지는않았다 [11,12]. 미생물학적검사수많은세균이 parapneumonic effusion이나 empyema의원인이지만특히혐기성균의증명은어려운경우가많다. 부패성냄새 (putrid odor) 가있으면혐기성세균에의한농흉의가능성이많으며, 그람염색이도움이된다. 혐기성세균은농흉의 36-76% 에서만증명되며, Fusobacterium nucleatum, Prevotella sp, Peptostreptococcus, Bacteroides fragilis group 이주된원인균으로알려져있다 [13,14]. 그러므로농흉의경우에혐기성세균이확인되지않았다고하더라도혐기성세균에도효과적인항생제를사용하는것이도움이된다 [15]. 그외에도농흉에서흔히발견되는세균은 Streptococcus milleri, Staphylococcus aureus, Enterobacteriaceae 등이며, 당뇨환자에서는 Klebsiella pneumonia 감염에의해서도농흉이흔히발생한다 [16]. 인플루엔자감염합병증으로발생하는농흉에서는 S. aureus, S. pneumoniae, S. pyogenes 등이주된원인균이다 [17]. 항생제치료에반응하지않아서 video-assisted thoracoscopic drainage를시행한 234명의 complicated parapneumonic effusion 환자들에서발견된원인균은 Streptococcus pneumoniae (20%), Staphylococcus aureus (21%), coagulase negative staphylococcus (17%), Pseudomonas (14%), Klebsiella (10%) 였다 [18]. Complicated pleural effusion의치료흉강천자등을통해합병부폐렴삼출이나농흉으로진단되면, 적절한항생제치료가중요하며, 잘치료되지않는경우에는흉관배액 (chest tube drainage) 또는경피도관배액 (percutaneous catheter drainage) 이필요하게되고, 섬유소용해물질 (fibrinolytic agent) 이선택적으로사용된다. 이러한치료에도불구하고적절한배액이이루어지지않을경우흉강경수술 (video-assisted thoracoscopic surgery, VATS), 겉질제거 (decortication) 등의외과적수술이시행되기도한다. 최근에 는항생제의개선과섬유소용해물질사용의보편화등으로치료성적의향상이있었으나농흉의경우는아직도 20% 이상의높은사망률을보인다 [19]. 항생제선택가장중요한원칙의원인질환인폐렴의가장가능성이높은원인균에대한적절한항생제를경험적으로또는미생물검사결과를바탕으로치료하는것이다. 대부분의항생제는늑막강내로잘침투하지만, ph가낮은흉막삼출액내에서는 aminoglycoside 계통의항생제는효과가없을수있음을염두에두어야한다 [20]. 혐기성세균이 complicated pleural effusion 또는농흉의원인균인경우가많으며증명되지않는경우가많으므로혐기성세균도치료할수있는경험적항생제치료가권장되며, 일반적으로 clindamycin, beta-lactam plus beta-lactamase inhibitors (amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam), carbapenems (imipenem, meropenem, or ertapenem) 등이사용되지만, penicillin 또는 metronidazole 등의단독요법은권장되지않는다. Complicated parapneumonic effusion (category 3 in the ACCP consensus guidelines) (Table 1) 은항생제치료에반응하지않는경우가많다 [8]. 그러므로조기에모든소방성흉막삼출액을흉관배액하는것이치료효과를높이고입원기간을줄이는방법으로여겨지고있지만 [21], 아직까지전향적연구로확인되지는않았다. 또한다수의 loculated pleural effusion 에서는필요한경우여러개의흉관튜브를삽입하여신속하게배액하는것이필요할수있다. 흉관배액술로호전되지않는경우에는항생제치료가부적절하였거나흉관배액술치료중에합병되는소방성농흉을의심하여야한다. 추적 CT 검사나영상검사에서흉막삼출액의배액이불충분한경우에는 video-assisted thoracoscopic surgery (VATS) 를통하여죽은조직제거술 (debridement) 과배액을추가로시행하는것이필요하다. 농흉의치료농흉 (category 4 in the ACCP consensus guidelines) 은 [8], 필요하다면조기에적절한또는개흉죽은조직제거술 (open thoracotomy ebridement) 과배액을고려하여야한다 [22]. 적절한농흉의치료과정은우선최소한 4-6주이상의적합한항생제치료를시행하여농흉내의세균감염을치료하고, 흉관배액량이최소한으로될때까지기다리고 CT로더이상의 - 145 -
- 대한내과학회지 : 제 81 권제 2 호통권제 612 호 2011 - Table 1. Categorizing risk for poor outcome in patients with parapneumonic effusions Pleural space anatomy Pleural fluid bacteriology A0 Minimal, free flowing (< 10 AND Bx Culture and Gram AND mm on lat decub film) b stain results unknown A1 Small to moderate free flowing effusion (> 10 mm and < 1/2 hemithorax) A2 Large, free flowing ( 1/2 hemithorax) f, loculated effusion g, or effusion with thickened parietal pleura h Pleural fluid chemistry a Category Risk of poor outcome Drainage AND Cx ph unknown 1 Very low No c AND B0 Neg culture and Gram stain e AND C0 ph 7.20 2 Low No d OR B1 Positive culture or Gram stain OR C1 ph < 7.20 3 Moderate Yes B2 Pus 4 High Yes a ph is the preferred pleural fluid chemistry test, and ph must be determined by a blood gas analyzer. If a blood gas analyzer is not available, pleural fluid glucose should be used (P0, glucose 60 mg/dl; P1, glucose < 60 mg/dl). The expert panel cautions that the clinical utility and decision thresholds for ph and glucose have not been well-established. b Clinical experience indicates that effusions of this size do not require thoracentesis for evaluation, but will resolve. c If thoracentesis were performed in a patient with A0 category pleural anatomy and P1 or B1 status found, clinical experience suggests that the P1 or B1 findings might be false-positive. Repeat thoracentesis should be considered if effusion enlarges and/or clinical condition deteriorates. d If clinical condition deteriorates, repeat thoracentesis and drainage should be considered. e Regardless of prior antibiotic use. f Larger effusions are more resistant to effective drainage, possibly because of the increased likelihood that large effusions will also be loculated. g Pleural loculations suggest a worse prognosis. h Thickened parietal pleura on contrast-enhanced CT suggests presence of empyema. Adapted from Colice, GL, Curtis, A, Deslauriers, J, et al., Chest 2000;118:1158. 농흉이남아있지않음을확인하며, 농흉강이없어져서폐가완전히펴질때까지치료하는것이다. 농흉의배액농흉의배액방법은 tube thoracostomy, video-assisted thoracoscopic surgery (VATS), open decortication 과 open thoracostomy가사용될수있다. 흉관배액 (tube thoracostomy drainage) 은농흉액의배액에서가장덜침습적인방법이다. 이방법은단일소방농흉에서주로효과적인치료방법이지만다방성농흉에서도흔히시도되는치료방법이다. 흉관의삽입위치는 CT나초음파검사를이용하여결정하는것이안전하고효과적이다. 다방성농흉에서는주로소구경의여러개의흉관을삽입하여각각의소방성농흉을배액하는것이좋다. 일반적으로단일소방농흉에서는구경이큰흉관을삽입하는것이효과적인것으로여겨져왔지만, Multi-center Intrapleural Streptokinase Trial (MIST1) 에서대구경 (15-20F), 중간구경 (10-14F), 또는소구경흉관 (< 10F) 사용여부에따른치료성공률이나사망률의차이가없었으나, 흉관배액술시에소구경흉관을사용하는경우통증및합병증의빈도는유의하게낮았다 [23,24]. 소구경흉관을사용하는경우튜브가막힐가능성이높다는점이우려되었으나주기적으로흉관내강을생리식염수로세정 (30 ml of sterile saline every 6 hours via a three way valve) 해주는방법이 British Thoracic Society guideline 에서는권장되고있다 [25]. 농흉의배농을위한흉관삽입후 24시간이내에 CT를촬영하여흉관의위치가적절한지여부를확인하는것이도움이되며, 배농되는양이 50 ml/day 이하로감소하고농흉강이폐쇄될때까지유지한다. 섬유소용해제요법흉강내섬유소용해제요법 (streptokinase, urokinase, tissue plasminogen activator [TPA]) 은 loculated parapneumonic effusion 과농흉의배액을위해사용되어왔으나여러연구들에서효과에대한주장이상반되고있다. 그러나현재까지섬유소 - 146 -
- 김석찬. 합병성흉막삼출액의진단및치료 - 용해치료는흉관배액이잘안되고흉수가많이차있는증상이있는환자에서는효과가있을수있으며, 새로운약제인 deoxyribonuclease 를사용하면농흉의점성이감소하여배액이잘되기때문에섬유소용해제와병합투여할수있다. 특히외과적인배액을하기어렵고지속적인패혈증이있는환자에서도사용해볼수있다 [26]. 기존의연구들의연구방법과약제의투여방법에문제가있어서아직은섬유소용해요법의효과에대한결론을내리기힘들며, 현재 TPA를사용하는대규모임상연구가진행중이다. 흉강경하죽은조직제거술 (thoracoscopic debridement) Video-assisted thoracoscopic surgery (VATS) 를이용하여 complicated pleural effusion 특히 uni-or multi-loculated empyema 를치료할수있다 [27]. 농흉의 VATS 치료시도중에치료가어려울경우에는개흉술로바로전환하여적절한조치를취할수있다는것이장점이다. VATS 시도하였으나결국은개흉술이필요한경우는 44% 에서 3% 정도까지다양하다 [28,29]. 개흉 decortication이필요하게되는위험인자는치료가지연되었을경우와그람음성균에감염된농흉인경우이다. 겉질제거 (decortications) 흉막의비후는흉막염이치료되고나면점진적으로호전되지만, 장측흉막의비후가호전되지않으면서폐가다시펴지지않으면농흉강이형성된경우가많다. 이런경우에는겉질제거가필요하게된다 [30]. 흉강경하겉질제거의치료성적은개흉겉질제거의성적과비슷하다 [31]. 흉막유착이심하고, 장측흉막의비후가심하고, 농흉의크기가큰경우에는개흉겉질제거를선호하는경향이많다 [32]. Open thoracostomy Open thoracostomy 는농흉강의하부에서배액이되도록늑골의일부를절제하고흉강에계속적인배농이되도록입구를만들어놓는수술로서우선은흉관을삽입한채로유지하다가 60-90일정도지나면입구가안정되게남아있게된다. Open thoracotomy 는겉질제거보다는덜침습적인수술로서환자의상태가좋지않을때선택할수있는치료법이다. 일차치료에반응하지않는증상이있는비악성흉막삼출액의치료흉막삼출액은원인에대한치료가가장중요하며, 대개 호전되지만악성흉수가아님에도불구하고일부에서는치료에반응하지않고계속흉막삼출액이지속되는경우가있다. 이런경우증상이있는경우라면일반적으로반복적인흉막천자또는흉막유합 (pleurodesis) 이필요할수있다. 그외에다른치료방법으로간헐적인흉막배액을위한 indwelling pleural catheter를삽입하거나, pleurectomy 또는 pleural-peritoneal shunt 등의특수한치료가필요할수도있다. 치료대상일차치료에반응하지않는흉막삼출액으로서호흡곤란등의증상이있는경우에치료대상이될수있다. 일차치료외에좀더침습적인치료를고려하기전에우선흉막삼출액의원인을다시확인하고, 폐의허탈로인해흉막삼출액이소실되지않는지를먼저확인하여야한다. 증상이없는경우에는아래와같은침습적인치료들을시도할필요가없다. 치료방법반복적인흉수천자반복적인흉수천자는흉수의증가속도가느려서, 한번흉수천자를시행하고상당기간이지나서야다시흉수천자가필요한경우에적절하다. 자주흉수천자가필요하여반복적시술의위험성이증가하거나환자의불편함이증가한다면다른치료방법을시도하는것이좋다. 대개한달에 1번정도의흉수천자로잘조절이되는경우라면시도해볼수있는치료방법이다. 대개한번시술시 1-1.5 L의흉수를천천히배액하는것이적절하다. 흉수배액이너무빨리되면, reexpansion pulmonary edema가합병증으로발생할수있는데, 이런합병증은매우드물며, 배액중에환자가흉통을호소하거나흉막압이 -20 cmh 2O로떨어지면배액을중단하는것만으로도방지할수있다 [33]. 합병증을방지하기위해권장되는배액속도는아직까지알려진바없으며, 시술중에환자를관찰하는것이가장좋은방법이다 [33]. 그외에발생할수있는합병증은배액중에발생하는기흉으로서배액중에폐가다시펴지지않는경우에발생할수있다 [34]. 흉막유합 (Pleurodesis) 흉막유합은흉막액을배액한후에흉막강을폐쇄시켜더이상의반복적인흉막액저류를방지하기위한시술로서 talc가가장많이사용되는약제이다. 다른약제로는 tetracycline, minocycline, doxycycline, silver nitrate, iodopovidone, bleomycin, - 147 -
- The Korean Journal of Medicine: Vol. 81, No. 2, 2011 - Corynebacterium parvum with parenteral methylprednisolone acetate, erythromycin, fluorouracil, interferon beta, mitomycin C, cisplatin, cytarabine, doxorubicin, etoposide 등이시도되고있다. 그러나약제의생산중단및 talc의경우발암물질로서의위험성등으로인해제한점이있는점등을고려하여적절한약제를선택하여시술한다 [35-40]. 흉막유합은증상이있으며반복적인흉수천자에도불구하고수일내지일주일이내에다시흉수저류가발생하는환자에서권장되며, 대개치료성적은 50-70% 정도의성공률을보이는것으로알려져있다 [41-44]. 흉막유합은폐가다시펴지지않는경우에는시술할수없으며, 흉막내감염증으로인한반복적인흉막삼출액에서도사용할수없다. 흉막유합의드문합병증은호흡부전, 심혈관계합병증, 전신염증반응, 농흉, 폐용적의감소와흉막유합에사용된약제에의한전신반응등이있으며, 대부분의합병증은악성흉막삼출증에서보고되었지만비악성흉막삼출증에서도일어날수있으므로주의를요한다. 그외에도 talc를사용한경우에급성호흡부전및오랜시간이경과후발생할있는늑막석회화및악성종양의가능성에대한우려도보고되고있다 [45,46]. 기타치료방법 Indwelling pleural catheter for intermittent external drainage나 pleuroperitoneal 또는 pleurovenous shunts for internal drainage 또는 surgical pleurectomy가고려될수있다 [47,48]. 중심단어 : 부폐렴흉막삼출액 ; 농흉 ; 진단 ; 치료 REFERENCES 1. Light RW, Girard WM, Jenkinson SG, George RB. Parapneumonic effusions. Am J Med 1980;69:507-512. 2. Heffner JE, Klein JS, Hampson C. Diagnostic utility and clinical application of imaging for pleural space infections. Chest 2010; 137:467-479. 3. Moskowitz H, Platt RT, Schachar R, Mellins H. Roentgen visualization of minute pleural effusion. An experimental study to determine the minimum amount of pleural fluid visible on a radiograph. Radiology 1973;109:33-35. 4. Woodring JH. Recognition of pleural effusion on supine radiographs: how much fluid is required? AJR Am J Roentgenol 1984;142:59-64. 5. Aquino SL, Webb WR, Gushiken BJ. Pleural exudates and transudates: diagnosis with contrast-enhanced CT. Radiology 1994;192:803-808. 6. Waite RJ, Carbonneau RJ, Balikian JP, Umali CB, Pezzella AT, Nash G. Parietal pleural changes in empyema: appearances at CT. Radiology 1990;175:145-150. 7. Kearney SE, Davies CW, Davies RJ, Gleeson FV. Computed tomography and ultrasound in parapneumonic effusions and empyema. Clin Radiol 2000;55:542-547. 8. Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest 2000;118:1158-1171. 9. Heffner JE, Brown LK, Barbieri C, DeLeo JM. Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis. Am J Respir Crit Care Med 1995;151:1700-1708. 10. Sahn SA. State of the art. The pleura. Am Rev Respir Dis 1988;138:184-234. 11. 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. 12. Porcel JM. Pleural fluid tests to identify complicated parapneumonic effusions. Curr Opin Pulm Med 2010;16:357-361. 13. Boyanova L, Vladimir D, Gergova G, et al. Anaerobic microbiology in 198 cases of pleural empyema: a Bulgarian study. Anaerobe 2004;10:261-267. 14. Civen R, Jousimies-Somer H, Marina M, Borenstein L, Shah H, Finegold SM. A retrospective review of cases of anaerobic empyema and update of bacteriology. Clin Infect Dis 1995;20 Suppl 2:S224-S229. 15. Brook I, Frazier EH. Aerobic and anaerobic microbiology of empyema. A retrospective review in two military hospitals. Chest 1993;103:1502-1507. 16. Chen KY, Hsueh PR, Liaw YS, Yang PC, Luh KT. A 10-year experience with bacteriology of acute thoracic empyema: emphasis on Klebsiella pneumoniae in patients with diabetes mellitus. Chest 2000;117:1685-1689. 17. Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008;198:962-970. 18. Luh SP, Chou MC, Wang LS, Chen JY, Tsai TP. Video-assisted thoracoscopic surgery in the treatment of complicated parapneumonic effusions or empyemas: outcome of 234 patients. Chest 2005;127:1427-1432. 19. Kelly JW, Morris MJ. Empyema thoracis: medical aspects of evaluation and treatment. South Med J 1994;87:1103-1110. 20. Vaudaux P, Waldvogel FA. Gentamicin inactivation in purulent exudates: role of cell lysis. J Infect Dis 1980;142:586-593. 21. Berger HA, Morganroth ML. Immediate drainage is not required for all patients with complicated parapneumonic effusions. Chest - 148 -
- Seok Chan Kim. Diagnosis and treatment of complicated pleural effusion - 1990;97:731-735. 22. Wozniak CJ, Paull DE, Moezzi JE, et al. Choice of first intervention is related to outcomes in the management of empyema. Ann Thorac Surg 2009;87:1525-1530; discussion 1530-1531. 23. Maskell NA, Davies CW, Nunn AJ, et al. Controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med 2005;352:865-874. 24. Rahman NM, Maskell NA, Davies CW, et al. The relationship between chest tube size and clinical outcome in pleural infection. Chest 2010;137:536-543. 25. Roberts HS. BTS guidelines for the management of pleural infection. Thorax 2004;59:178; author reply 178. 26. Tokuda Y, Matsushima D, Stein GH, Miyagi S. Intrapleural fibrinolytic agents for empyema and complicated parapneumonic effusions: a meta-analysis. Chest 2006;129:783-790. 27. Potaris K, Mihos P, Gakidis I, Chatziantoniou C. Video-thoracoscopic and open surgical management of thoracic empyema. Surg Infect (Larchmt) 2007;8:511-517. 28. Lardinois D, Gock M, Pezzetta E, et al. Delayed referral and gram-negative organisms increase the conversion thoracotomy rate in patients undergoing video- assisted thoracoscopic surgery for empyema. Ann Thorac Surg 2005;79:1851-1856. 29. Wurnig PN, Wittmer V, Pridun NS, Hollaus PH. Video-assisted thoracic surgery for pleural empyema. Ann Thorac Surg 2006; 81:309-313. 30. Chan DT, Sihoe AD, Chan S, et al. Surgical treatment for empyema thoracis: is video-assisted thoracic surgery "better" than thoracotomy? Ann Thorac Surg 2007;84:225-231. 31. Tong BC, Hanna J, Toloza EM, et al. Outcomes of video-assisted thoracoscopic decortication. Ann Thorac Surg 2010;89:220-225. 32. Striffeler H, Gugger M, Im Hof V, Cerny A, Furrer M, Ris HB. Video-assisted thoracoscopic surgery for fibrinopurulent pleural empyema in 67 patients. Ann Thorac Surg 1998;65:319-323. 33. Doelken P, Huggins JT, Pastis NJ, Sahn SA. Pleural manometry: technique and clinical implications. Chest 2004;126:1764-1769. 34. Heidecker J, Huggins JT, Sahn SA, Doelken P. Pathophysiology of pneumothorax following ultrasound-guided thoracentesis. Chest 2006;130:1173-1184. 35. Tan C, Sedrakyan A, Browne J, Swift S, Treasure T. The evidence on the effectiveness of management for malignant pleural effusion: a systematic review. Eur J Cardiothorac Surg 2006;29: 829-838. 36. Yoshida K, Sugiura T, Takifuji N, et al. Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515. Lung Cancer 2007;58:362-368. 37. Balassoulis G, Sichletidis L, Spyratos D, et al. Efficacy and safety of erythromycin as sclerosing agent in patients with recurrent malignant pleural effusion. Am J Clin Oncol 2008;31:384-389. 38. Agarwal R, Paul AS, Aggarwal AN, Gupta D, Jindal SK. A randomized controlled trial of the efficacy of cosmetic talc compared with iodopovidone for chemical pleurodesis. Respirology 2011 May 23 [Epub]. DOI: 10.1111/j.1440-1843.2011.01999.x. 39. Salomaa ER, Pulkki K, Helenius H. Pleurodesis with doxycycline or Corynebacterium parvum in malignant pleural effusion. Acta Oncol 1995;34:117-121. 40. Terra RM, Kim SY, Pego-Fernandes PM, Teixeira LR, Vargas FS, Jatene FB. Is silver nitrate pleurodesis for patients with malignant pleural effusion feasible and safe when performed in an outpatient setting? Ann Surg Oncol 2011;18:1145-1150. 41. Steger V, Mika U, Toomes H, et al. Who gains most? A 10-year experience with 611 thoracoscopic talc pleurodeses. Ann Thorac Surg 2007;83:1940-1945. 42. Sudduth CD, Sahn SA. Pleurodesis for nonmalignant pleural effusions. Recommendations. Chest 1992;102:1855-1860. 43. Glazer M, Berkman N, Lafair JS, Kramer MR. Successful talc slurry pleurodesis in patients with nonmalignant pleural effusion. Chest 2000;117:1404-1409. 44. Herrington JD, Gora-Harper ML, Salley RK. Chemical pleurodesis with doxycycline 1 g. Pharmacotherapy 1996;16:280-285. 45. Light RW. Talc should not be used for pleurodesis. Am J Respir Crit Care Med 2000;162:2024-2026. 46. Sahn SA. Talc should be used for pleurodesis. Am J Respir Crit Care Med 2000;162:2023-2024; discussion 2026. 47. Schneider T, Reimer P, Storz K, et al. Recurrent pleural effusion: who benefits from a tunneled pleural catheter? Thorac Cardiovasc Surg 2009;57:42-46. 48. Artemiou O, Marta GM, Klepetko W, Wolner E, Muller MR. Pleurovenous shunting in the treatment of nonmalignant pleural effusion. Ann Thorac Surg 2003;76:231-233. - 149 -