Is blood pleurodesis effective for determining the cessation of persistent air leak?

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1 doi: /icvts Interactive CardioVascular and Thoracic Surgery 11 (2010) Best evidence topic - Thoracic non-oncologic Is blood pleurodesis effective for determining the cessation of persistent air leak? a b b b, Anthony Chambers, Tom Routledge, Andrea Billè, Marco Scarci * a Brighton and Sussex Medical School, BSMS Teaching Building, University of Sussex, Brighton, East Sussex BN1 9PX, UK b Department of Thoracic Surgery, Guy s Hospital, Great Maze Pond, London SE1 9RT, UK Received 2 February 2010; received in revised form 13 June 2010; accepted 24 June Summary A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed whether blood pleurodesis is effective for cessation of persistent air leak (PAL). Altogether more than 43 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that autologous blood pleurodesis has superior outcomes when compared with conservative management for treatment of postoperative PAL. In addition, for PAL causing pneumothorax, blood pleurodesis woptimal volume 100 ml (from two studies)x should be considered in patients who are unsuitable for surgery, talc pleurodesis is ineffective or not viable (including cases complicated by acute respiratory distress syndrome) and a prompt resolution is required. Some 70 81% of patients treated for postoperative air leak resolved within 12 h and % within 48 h vs. a mean of days (from two studies) with simple drainage. Resolution of pneumothorax with blood pleurodesis was also significantly shorter (P-0.01). Overall success rates (from all studies) were 92.7% (ns133) from patients having undergone pulmonary surgery (76.6% in one injection, ns111), and 91.7% (ns109) of patients with pneumothorax. Recurrence rates were between 0 and 29% compared with 35 41% for simple drainage, although one controlled study in which the recurrence rate was improved from 16% in controls to 0% in the blood pleurodesis group (at months). Minor complication (empyemayfeverypleural effusion) rates varied between studies (0 18%), although they show reduced incidence in line with improving technique over time. A controlled study looking at acute respiratory distress syndrome complicated by pneumothorax showed a significant reduction in mortality (odds ratio 0.6), time to cessation of air leak (P-0.01), weaning time (P-0.01) and intensive treatment unit (ITU) stay (P-0.01) whilst another randomized control study showed significant reduction in hospital stay following pulmonary resection (P-0.001) Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Blood pleurodesis; Blood patch; Airleaks; Pneumothorax 1. Introduction A best evidence topic was constructed according to a structured protocol. This is fully described in ICVTS w1x. 2. Three-part question In wpatients with persistent air leakx is wblood pleurodesisx effective for wdetermining cessation of air leakx? 3. Clinical scenario A 75-year-old man is on your ward following a right upper lobectomy. He is seven days postoperative and has persistent air leak (PAL), which you believe is due to emphysematous lung disease. The patient could be discharged; however, you are concerned about drain management outside of hospital. You wonder whether a blood pleurodesis would be a suitable treatment to shorten the length of stay and minimize potential complications. *Corresponding author. Tel.: q address: marco.scarci@mac.com (M. Scarci) Published by European Association for Cardio-Thoracic Surgery You decide to carry out a literature search for the evidence. 4. Search strategy wexp pleurodesisyor blood pleurodesis.mpx AND wpulmonary surgical procedures.mp OR OR exp pneumothoraxx AND wexp postoperative complicationsyor air leak.mpx Medline 1950 to Jan 2010 using OVID interface. 5. Search outcome Forty-three papers were found using the reported search. From these, 10 papers were identified that provided the best evidence to answer the question. These are presented in Table Results Robinson w2x conducted the first study of blood pleurodesis for PAL in Twenty-five patients were treated, as a result of adhesions holding open a bulla causing chronic

2 A. Chambers et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) Table 1. Best evidence papers Robinson, (1987), 25 patients with Air leak cessation 85% (21 patients) This was the first study Can J Surg, persistent air leak to consider autologous Canada, w2x causing chronic Complications 0 (0%) blood pleurodesis as an pneumothorax treated alternative to chemical Prospective with autologous blood pleurodesis or surgery cohort study pleurodesis (level 1b) Dumire et al., Two cases in which Recurrence rate Chest tube removed at 72 h and no 50 ml of blood added (1992), Chest, patients with a recurrence at 16 months after tetracycline USA, w3x prolonged air leak who pleurodesis was were not candidates ineffective Case study for thoracotomy had (level 3b) immediate treatment with an autologous blood patch pleurodesis Cagirici et al., From a prospective Air leak cessation Pleurodesis: 27 patients (84%) Increased intrathoracic (1998), Scand study series of 167 within 72 h infection rate seen with Cardiovasc J, patients with tube pleurodesis but is Turkey, w4x thoracostomy for Air leak duration Decreased with pleurodesis (P-0.01) painless and more spontaneous compared with simple drainage effective than simple Prospective pneumothorax in drainage cohort study , 32 Complications with Empyema: three patients (9%) (level 1b) patients (age range pleurodesis Minor complications (feverypleural years, mean effusion): nine patients (28%) age 45.5 years) were treated with autologous Recurrence Pleurodesis: 0 patients blood-patch Simple drainage: 22 patients (16%) pleurodesis for persistent air leak Ando et al., (1999), 11 patients treated for Recurrence rates Success Failure Injections to deflated Respir Med, Japan, 17 occurrences of (success: air leak lungs required two w5x pneumothorax with cessation within two Inflated 6 4 injections in 75% of persistent air leak days of injection) lung successful cases Prospective comparing injection compared with 33% cohort study pre- and postblood Deflated 4 3 of inflated lungs (level 1b) injection lung Recurrence Two patients (18%) Rivas de Andres, Between June 1993 Success rate 100% (six patients) One patient died of (2000), Ann and January 1998, (mean follow-up cerebral metastasis 50 Thorac Surg, pleurodesis with 26.1 months) days postpleurodesis Spain, w6x autologous blood performed in six patients Volume of blood ml (median 100 ml) Prospective who had air leak )10 injected cohort study (mean 16.3) days (level 1b) following non-small cell lung cancer Best Evidence Topic Lang-Lazdunski 11 patients operated Air leak cessation 72.7% (eight patients) Strict adhesion to and Coonar, (2004), on by a single surgeon within 12 h contraindications and Eur J Cardiothorac between January 2002 a single injection of a Surg, UK, w7x and January 2004 Air leak cessation 100% limited volume of blood presenting with a within 48 h advocated to minimize Prospective persistent air leak after the risk of serious cohort study pulmonary resection Volume of blood 50 ml (in all cases) infectious complications, (level 2b) treated by autologous injected such as empyema blood patch pleurodesis Complications Pneumonia (one patient) Low-grade fever (two patients) (Continued on next page)

3 470 A. Chambers et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) Table 1. (Continued) Ozpolat, (2010), Between 1997 and Air leak cessation 20 of 24 patients (83%) This is the first report Thorac Cardiovasc 2007, autologous blood within 24 h in the literature on the Surg, Turkey, w8x patch pleurodesis was use of this method after used to treat prolonged Air leak cessation 21 of 24 patients (87%) hydatid cyst surgery Reterospective air leak in 24 patients. cohort study Prolonged air leak was Complications 0% (level 2b) due to spontaneous pneumothorax in 17 patients and secondary to pulmonary hydatid cyst operation in seven patients Martinez-Escobar Participants were two Control group Blood P-value In addition, the blood et al., (2006), groups of 27 patients, (simple drainage) pleurodesis pleurodesis group J Crit Care, all with ARDS, Mean (range) Mean (range) shows an improvement Spain, w9x pneumothorax, and in respiratory PAL, matched 1:1 Sealing time (days) 10 (4 16) 2 (1 5) parameters; a smaller Case-control for risk factors and number of events of study either given autologous Weaning time 16 (8 26) 5 (2 12) haemodynamic (level 3b) blood pleurodesis or from ventilation instability; and less need conventional chest (days) for tracheostomy drainage with water compared with controls seal Intensive care unit 29 (16 47) 16 (8 62) for tracheostomy time (days) Death Blood pleurodesis odds ratio: 0.6 ( ) Droghetti et al., During a seven-year Volume of blood 50 ml two patients No pain, respiratory (2006), experience, 21 patients injected 100 ml six patients difficulty, cough, or J Thorac Cardiovasc submitted to 150 ml 13 patients major side effects were Surg, Italy, w10x pulmonary resection observed during the were postoperatively Number of injection procedure. No Retrospective treated with an significant decrease in cohort study autologous blood patch Air leak cessation 1 2 haematocrit value was (level 2b) for persistent air leaks -12 h 15 (81%) observed after removal -24 h 17 (100%) of blood but in contrast 48 h 100% to earlier studies higher volumes of blood were Major complications 0 (0%) necessary to seal the air leak Minor complications Fever; 2 (10%) Prolonged pleural effusion; 1 (5%) Relapse; 0 (0%) Shackcloth et al., 20 patients randomly Variable Study Control P-value This technique is (2006), assigned to one of two Median (IQR) group group effective in sealing air Ann Thorac Surg, treatment pathways. Days Postoperative leaks after lobectomy. It UK, w11x The study group allows earlier chest drain received instillation of Time to leak seal 5 (5 7) 11(10 12) removal and shortens Prospective 120 ml autologous (days) hospital stay randomized trial blood into their apical (level 1b) chest drain on the fifth Time to drain 6.5 (6 8) 12 (11 13) postoperative day, removal (days) and again if the air leak persisted on days 7 Time to hospital 8 (7 9) 13.5 (12 14) and 9, respectively. discharge (days) The control group continued to be treated Interval from first 1 (1 3) 3 (1 4) 0.32 by tube thoracostomy pleurodesis to alone, but if the air seal of air leak leak was still present on the 10th postoperative day they crossed over and (Continued on next page)

4 A. Chambers et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) Table 1. (Continued) underwent intrapleural installation of blood as in the study group Andreetti et al., 25 patients with air Group A Group B Group C Other complications (2007), J Thorac leaks on the sixth (50 ml (100 ml (simple namely, fever and Cardiovasc postoperative day blood) blood) drainage) colonization of the Surg, Italy, w12x after lobectomy were pleural fluid, were not enrolled in this study. Air leak cessation 2.3" " "3.7 observed in our study. Randomized They were randomly (mean) days Careful sterile case study assigned to two groups: manipulation of the (level 1b) group A (12 patients), P-value A and B (Ps0.005), system during the with 50 ml of A and C (Ps0.0009), procedure should be autologous blood B and C (Ps0.0001) stressed to avoid infused in the pleural infectious cavity; and group B complications. (13 patients), with Pleurodesis with an 100 ml of blood autologous blood patch, infused. These two is easy to perform, safe, groups were and effective, and does retrospectively not add costs. It can be compared with the last used as a first-line 15 patients showing manoeuver to solve this the presence of air common and unpleasant leaks for at least 6 days problem Athanassiadi et al., 20 patients (14 male Air leak cessation within: All types of lung (2009), Thorac and six female) surgery studied here Cardiovasc Surg, underwent blood 12 h 14 (70%) (LVRS, lobectomy, Germany, w13x pleurodesis due to secondary persistent air leak ()7 24 h 17 (85%) pneumothorax) show Prospective days). Lobectomy was equivocal results for cohort study performed in 10 cases, 48 h 19 (95%) correction of the air leak (level 1b) LVRS in four and three with blood pluerodesis patients suffered Reoperation One patient with lung secondary from volume reduction pneumothorax. surgery and in two Autologous blood cases was a second pleurodesis was instillation of blood performed at bedside performed IQR, inter-quartile range; LVRS, lung volume reduction surgery. pneumothorax, with one to three injections of autologous blood and a success rate of 85% (21 patients) and without any complications. Dumire et al. w3x followed with two cases of PAL in 1992, reporting blood patch pleurodesis as effective, simple and inexpensive as a last resort therapy. In 1998, Cagirici et al. w4x conducted a prospective study evaluating efficacy of autologous blood pleurodesis in 32 patients, following tube thoracostomy for spontaneous pneumothorax. Cessation of the air leak occurred within 72 h in 27 patients (84%) and showed reduced duration compared with simple drainage (P-0.01). Minor complications (feverypleural effusion) occurred in nine patients (28%) although no recurrence was seen in the 48-month follow-up compared with 22 patients undergoing simple drainage (16%). Ando et al. w5x followed this with a comparative study of injection of autologous blood on both inflated and deflated lungs in 17 cases of pneumothorax with PAL, for which resolution occurred in 60% (six patients) and 57% (four patients), respectively. Repeat injection was required for success in 75% of deflated lung cases compared with 33% of inflated lung cases. Two recurrences were seen at twoyear follow-up in all groups. In 2000, Rivas de Andres et al. w6x evaluated blood pleurodesis for PAL (mean 16.7 days) in six patients following surgery for non-small cell lung cancer with 100% success rate using a median blood volume of 100 ml, for which no complications were reported. Building upon this study, prospective analysis by Lang-Lazdunski and Coonar w7x, assessed blood pleurodesis for PAL (mean 7.8 days) following lung resection in 11 patients. Using 50 ml of blood in each case, cessation of the air leak was achieved in 72.7% (eight patients) within 12 h and 100% within 48 h. Most recently, Ozpolat w8x reports the efficacy of blood patch pleurodesis for PAL following pulmonary hydatid cyst operations. Air leaks ceased in 21 of 24 patients with chest tube removal within 24 h if no leak was observed (20 patients). Martinez-Escobar et al. w9x conducted a case-control study to measure the effectiveness of blood pleurodesis for PAL in patients with acute respiratory distress syndrome com- Best Evidence Topic

5 472 A. Chambers et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) plicated by pneumothorax for which 27 cases were matched 1:1 with controls (thoracic drain and water seal). Mean sealing time for the pleurodesis group was two days compared with 10 days in the controls (P-0.01). Weaning time from ventilation was five days vs. 16 days w(p-0.01) odds ratio (OR); 0.1x and ICU time was 16 days vs. 29 (P-0.01, OR; 0.24) days for pleurodesis and controls, respectively. Death rates were also reduced when using blood pleurodesis (OR; 0.6). Droghetti et al. w10x experience of PAL (mean 11 days) following lung resection was retrospectively analysed in 21 patients treated with blood pleurodesis. Successful results were obtained from one injection in 81% (15 cases) within 12 h, and 100% (17 cases) within 24 h (mean 15 h, median 12 h, range 6 24 h). Those requiring two injections had 100% success at 48 h. No major complications were seen. Shackcloth et al. w11x (2006) conducted the first randomized prospective study of blood pleurodesis vs. tube thoracostomy following lobectomy in 22 patients. Successful cessation of the air leak occurred in 17 of the 29 occasions (58.6%; 95% CL: %) it was used, nine of 14 occasions in the study group (64.3%; 95% CL: %), and eight of 15 (53.3%; 95% CL: %) in the control group (Ps0.71). The median length of air leak was five days in the study group and 11 days in the control group (P-0.001). Time to chest drain removal (median 6.5 days vs. 12 days) and hospital discharge (median eight days vs days) were both significantly (P-0.001) shorter in the study group. Andreetti et al. w12x extended this further by randomizing patients receiving blood pleurodesis 50 ml (group A), 100 ml (group B) vs. standard drainage (group C). Air leaks ceased at 2.3"0.6 days (group A), 1.5"0.6 days (group B), and 6.3"3.7 days (group C). Groups A and B (Ps0.005), groups A and C (Ps0.0009), and groups B and C (Ps0.0001). Athanassiadi et al. w13x analysed 20 patients who had undergone lobectomy, lung volume reduction surgery or secondary pneumothorax correction. All PAL postoperatively gave equivalent results regardless of surgery type with 80% (14 patients) resolution within 12 h and 95% (19 patients) within 48 h. One patient required reoperation. 7. Clinical bottom line Currently, a number of methods are available to treat air leaks including prolonged tube thoracostomy, chemical pleurodesis, and surgical repair but there is little consensus on the role of blood pleurodesis. Here, several prospective studies (including two randomized control trials), show unanimously that autologous blood pleurodesis has superior outcomes for PALs in terms of sealing time, success rate and complication rates when compared with conservative treatment. Additionally, given the simple, inexpensive and painless nature of this bedside surgical procedure, blood pleurodesis should be considered for PAL. References w1x Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003;2: w2x Robinson CL. Autologous blood for pleurodesis in recurrent and chronic spontaneous pneumothorax. Can J Surg 1987;30: w3x Dumire R, Crabbe MM, Mappin FG, Fontenelle LJ. Autologous blood patch pleurodesis for persistent pulmonary air leak. Chest 1992; 101: w4x Cagirici U, Sahin B, Cakan A, Kayabas H, Buduneli T. Autologous blood patch pleurodesis in spontaneous pneumothorax with persistent air leak. Scand Cardiovasc J 1998;32: w5x Ando M, Yamamoto M, Kitagawa C, Kumazawa A, Sato M, Shima K. Autologous blood-patch pleurodesis for secondary spontaneous pneumothorax with persistent air leak. Respir Med 1999;93: w6x Rivas de Andres JJ, Blanco S, de la Torre M. Postsurgical pleurodesis with autologous blood in patients with persistent air leak. Ann Thorac Surg 2000;70: w7x Lang-Lazdunski L, Coonar AS. A prospective study of autologous blood patch pleurodesis for persistent air leak after pulmonary resection. Eur J Cardiothorac Surg 2004;26: w8x Ozpolat B. Autologous blood patch pleurodesis in the management of prolonged air leak. Thorac Cardiovasc Surg 2010;58: w9x Martinez-Escobar S, Ruiz-Bailen M, Lorente-Acosta MJ, Vicente-Rull JR, Martinez-Coronel JF, Rodriguez-Cuartero A. Pleurodesis using autologous blood: a new concept in the management of persistent air leak in acute respiratory distress syndrome. J Crit Care 2006;21: w10x Droghetti A, Schiavini A, Muriana P, Comel A, De Donno G, Beccaria M. Autologous blood patch in persistent air leaks after pulmonary resection. J Thorac Cardiovasc Surg 2006;132: w11x Shackcloth MJ, Poullis M, Jackson M, Soorae A, Page RD. Intrapleural instillation of autologous blood in the treatment of prolonged air leak after lobectomy: a prospective randomized controlled trial. Ann Thorac Surg 2006;82: w12x Andreetti C, Venuta F, Anile M, De Giacomo T, Diso D, Di Stasio M. Pleurodesis with an autologous blood patch to prevent persistent air leaks after lobectomy. J Thorac Cardiovasc Surg 2007;133: w13x Athanassiadi K, Bagaev E, Haverich A. Autologous blood pleurodesis for persistent air leak. Thorac Cardiovasc Surg 2009;57: