Doi:10.1016/j.ejcts.2004.08.034

Rapid pleurodesis in symptomatic malignant pleural effusion
Erkan Yildirim, Koray Dural, Rasih Yazkan, Nurullah Zengin, Dilsad Yildirim, Nesimi This information is current as of July 14, 2009
The online version of this article, along with updated information and services, is The European Journal of Cardio-thoracic Surgery is the official Journal of the European Associationfor Cardio-thoracic Surgery and the European Society of Thoracic Surgeons. Copyright 2005 by European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved. PrintISSN: 1010-7940. European Journal of Cardio-thoracic Surgery 27 (2005) 19–22 Rapid pleurodesis in symptomatic malignant pleural effusion* Erkan Yildirima,*, Koray Durala, Rasih Yazkana, Nurullah Zenginb, Dilsad Yildirima, Nesimi Gunala, Unal Sakincia aDepartment of Thoracic Surgery, Ankara Numune Education and Research Hospital, Ankara, Turkey bDepartment of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey Received 30 June 2004; received in revised form 5 August 2004; accepted 17 August 2004; Available online 19 November 2004 Objective: The objective of the study was to see whether a rapid method of pleurodesis was superior to the standard protocol in patients with symptomatic malignant pleural effusion. Methods: Between January 2000 and February 2003, a prospective randomised trial was carried out in asequential sample of 27 patients with malignant pleural effusions documented cytopathologically. Twelve patients were allocated to group 1(standard protocol) and 15 to group 2 (new protocol). A small-bore catheter (12 Fr) and oxytetracycline (35 mg/kg of body weight) were used inboth groups. In group 1, patients had drainage until radiological evidence of lung re-expansion was obtained and the amount of fluid drained wasless than 150 ml/day, before oxytetracycline was instilled. The catheter was removed when the amount of fluid drained after instillation wasless than 150 ml/day. In group 2, patients had the oxytetracycline instilled in a fractionated-dose manner following frequent aspirations at 6 hintervals. The catheter was removed when the total amount of fluid drained after instillation of the oxytetracycline [OT] was less than150 ml/last three aspirations. Response was evaluated at 1, 3 and 6 months after pleurodesis. Results: There was no statistically significantdifference in the demographic features, site of the primary tumour, disease characteristics, and response rates in any evaluation period in bothgroups (PO0.05). However, the number of days of drainage and hospitalisation, and the cost were significantly lower in the second group (P!0.001). Conclusions: This new pleurodesis method provided shorter hospital stay resulting in superior cost-effectiveness and palliation withoutsacrificing the efficacy of pleurodesis.
q 2004 Elsevier B.V. All rights reserved.
Keywords: Pleural diseases; Pleurisies; Malignant pleural effusion; Pleurodesis; Methods; Efficacy; Treatment effective palliation in these patients suffering from continu-ing challenges.
The management of patients with malignant pleural In the current study, we aimed at comparing the efficacy effusions can present significant diagnostic and therapeutic of the novel rapid pleurodesis method with the standard protocol. Fractionated doses of oxytetracycline (OT) were Symptomatic pleural effusions in patients with advanced administered with frequent aspirations of the pleural fluid at cancer is a common problem that causes significant 6 h intervals in an attempt to keep both pleurae in close morbidity and can negatively affect patients’ quality of life contact. The main objective of the present research was to for their remaining months. Several palliative treatment reduce the amount of time the patient should spend at the options are available. Repeated needle thoracocentesis, hospital after the intervention with equal efficacy.
tube thoracostomy, chemical or biologic pleurodesis, pleur-ectomy, and pleuroperitoneal shunt .
Pleurodesis aims to achieve a symphysis between parietal and visceral pleural surfaces, in order to prevent accumu-lation of fluid or air in the pleural space Rapid pleurodesis methods should be improved in the light of A prospective, randomised method was utilized to compare standard method of pleurodesis with the proposed * Presented at the joint 18th Annual Meeting of the European Association new rapid pleurodesis process in patients with symptomatic for Cardio-thoracic Surgery and the 12th Annual Meeting of the European malignant pleural effusion. The institutional review board Society of Thoracic Surgeons, Leipzig, Germany, September 12–15, 2004.
for human studies has approved the treatment protocols.
The procedures used were in accordance with the rec- Cankaya, Ankara, Turkey. Tel.: C90 312 482 72 79; fax: C90 312 310 34 60.
E-mail address: erseyda@yahoo.com (E. Yildirim).
ommendations found in the Helsinki Declaration of 1975.
1010-7940/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.ejcts.2004.08.034 E. Yildirim et al. / European Journal of Cardio-thoracic Surgery 27 (2005) 19–22 The same researchers performed all procedures in the same institution. The pathological diagnosis was proved by Characteristics of patient in both treatment groups either cytological examination of the pleural effusion or With their consents, patients were randomly assigned to one of two identified groups. The technique used in the first Z12) was the standard protocol and for the second group (nZ15) it was the new proposed method. A small-bore catheter (12 Fr) was used in both groups. The sclerosant agent used for the purpose of pleurodesis was OT (35 mg/kg of body weight) in both groups. The total dose of OT instilled in the pleural cavity was identical in both groups.
For the purpose of analgesia, prilocine; 1%, 20 cc (intrapleural, only single dose administration) and naproxen Values are expressed as absolute number of patients, and percentage in sodium 550 mg, tablet 2!1 (per os at least for the initial two or three days) were given to all of the patients included. This a MeanGSD (range); NS: Non-significant (PO0.05).
analgesia protocol sufficiently provided the required pain b Mortality within 6 months after treatment.
Patients in group 1 had catheter drainage until radiologi- continuous variables and the Chi-squared or Fischer’s exact cal evidence of lung re-expansion was obtained and the total tests for comparison of proportions at each group. Response amount of fluid drained was less than 150 ml/day, before OT rates between the two treatment methods were compared was instilled. The catheter was clamped for 6 h and then at each evaluation (1, 3 and 6 months) using Chi-squared opened to free drainage. It was removed when the amount of test. Time to recurrence and survival distributions was fluid drained after instillation of OT was less than analysed using the Kaplan–Meier Survival Analysis and Log Rank test. All statistical comparisons between the two Patients in group 2 also had small-bore catheter drainage, groups were carried out at the significance level of 0.05.
but the OT was instilled in a fractionated-dose mannerfollowing aspirations of the effusion at 6 h intervals. Inaverage, 383,61G113,60 ml of fluid per aspiration was removed every 6 h before each instillation of OT. All thefluid was aspirated at 6 h intervals either until the negative Demographic and primary disease characteristics are suction was achieved or before patients’ comfort level was summarized in . The majority of patients had breast compromised. The first dose was the half of the total cancer, lung cancer, and mesothelioma. Nearly 25% had calculated dose. And, the rest was instilled dividing into received prior systemic chemotherapy and 20–33% under- three equal amounts of doses after every aspiration. The went surgery for primary tumour. There were no significant catheter was clamped and left in place after administering differences between the two groups with regard to demo- each calculated doses of OT till the following aspiration step. The catheter was removed when the amount of fluid drained after completing the instillation of OT was totally Clinical and radiographic features were similar and in less than 150 ml/last three aspirations.
addition, morbidity of both procedures was statistically non-significant in both study groups.
Before pleurodesis, the size of the pleural effusion in a posteroanterior chest radiograph was catalogued as moder- ate, when extending from the diaphragm to the pulmonary hilum, and massive, when exceeding the hilar region.
Patients were followed up with chest radiographs at 1, 3 and 6 months after pleurodesis. Responses were classified (1) Complete (no clinical or radiological recurrence of pleural effusion); (2) partial (small amount of fluid reaccu- mulation in the chest radiograph, but no symptoms); (3) failure (reaccumulation of fluid causing symptoms or needing Both study groups were compared with respect to NE: not evaluable (death); CR: complete response, PR: partial response.
demographic and disease characteristics, and site of primary tumour. The t-test for independent samples was used for a For comparison of CR with PR and Failure combined.
E. Yildirim et al. / European Journal of Cardio-thoracic Surgery 27 (2005) 19–22 For a pleurodesis to be effective, firstly the lung must be fully expanded so that the parietal and visceral pleural surfaces are in apposition. Secondly, there must be good dispersion of the sclerosing agent throughout the pleuzral space. Moreover, the pleural spaces must be kept in close apposition after instillation of the agent for the chemical pleuritis to progress to pleural symphysis .
In the present clinical trial, the pleural fluid was aspirated manually at 6 h intervals to keep both pleurae in closeapposition before instillation of OT. The main purpose was to increase the contact duration and surface area of both pleurae for increasing the chemical pleuritis in the shortestpossible interval.
A trend for higher complete response rate was noted in The aspiration periods of the pleural effusion were the second group. Nevertheless, it was not statistically immediately followed by administration of OT. The total significant at 1, 3 and 6 months after pleurodesis dose of OT to be administered was calculated as 35 mg/kg of body weight The first fractionated dose, which was Pleural fluid pH and pleural fluid glucose levels were half of the total, was administered intrapleurally immedi- measured in group 1 and group 2 patients: 7.30G0.124 vs.
ately after the first aspiration. The rest was divided into 7.27G0.111 (PZ0.57) and 65.33G13.47 mg/dl vs. 65.00G three equal amounts and given consecutively after the 10.18 mg/dl, (PZ0.94), respectively. The results were sequential aspirations. These dosages are arbitrary, but statistically non-significant between both study groups.
seem to work well. The intra pleural dose of OT should be The mean volume of pleural fluid drained during the kept at a certain level to induce inflammatory and procedures was not significantly different in both groups.
fibrogenic effect on the pleurae as the drug is being In contrast, the mean day of drainage [7.00G3.04 vs.
partially absorbed by the pleura and decreasing the drug 1.867G4.85] and hospitalisation [8.33G4.85 vs. 2.33G 0.62] were significantly lower in the second group. The In conclusion, the findings of the current study showed results showed that the new proposed method was more that the new recommended method of 6 h aspiration cost-effective since patients spent less time at the hospital intervals with fractionated doses of OT resulted in reduced days of drainage and hospitalisation days rendering no more Six patients died in the first arm and five in the second morbidity than the standard procedure.
one, with a mean follow-up time of 5.5–6.4 months. There Further clinical studies need to be undertaken with larger was no significant difference in median survival period groups with a view to compare the efficacy of the OT with between the two treatment groups, 6.00 vs. 7.27 months, the other sclerosing agents using this novel pleurodesis Although not statistically significant, relapse occurred later in group 2 patients at a median time interval of 8.8months vs. 7.56 months.
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cheaper than sterile talc. Second, it was impossible to find [9] Sahn SA. Malignant pleural effusions. In: General thoracic surgery, 5th talc out of asbestos in Turkey, also more expensive. Lastly, ed. Lippincott Williams and Wilkins; 2000, p. 795–803.
[10] Wooten SA, Barbarash RA, Strange C, Sahn SA. Systemic absorption of OT was known to be well tolerated by the patients without tetracycline and lidocaine following intrapleural instillation. Chest 1988; E. Yildirim et al. / European Journal of Cardio-thoracic Surgery 27 (2005) 19–22 shows a good result in terms of pleurodesis. A trapped lung gives verybad results. So I think that the main point we have to consider intalking about pleurodesis and the type of pleurodesis, is if the lung we Dr S. Elia (Rome, Italy): What was the basic pathology? The survival changes even concerning the type of disease. If we’re are going to treat is a free lung or is it a trapped lung.
talking about lung cancer, it’s one matter. If we’re talking about Dr Yildirim: We had only 2 patients with entrapped lung in the breast cancer, it’s another point. So the survival end results of your first group and one patient in the second. As I’ve said, this is a small study have this type of bias, I think. What can you say concerning group of patients. These patients indeed did not benefit from this procedure and we had to perform thoracentesis and tube thoracost- Dr Yildirim: You mean the pathological types? Dr P.L. Filosso (Torino, Italy): We usually use talc for the Dr Yildirim: The basic disease was the breast cancer and the pleurodesis in this kind of patient. We have a large clinical experience using talc for pleurodesis in patients with malignant pleural effusions.
Dr Elia: And there was no difference between the two? Did you observe adverse side effects in using the tetracycline? Dr Yildirim: Yes. Of course, this study included a small group Dr Yildirim: We just had pleuritic pain, not any other side of patients and the study was going on at the moment, and we raised effects, and we could manage it by instilling prilocine 1% intrapleu- it to 40 patients, and again the results are the same.
rally before the procedures in both groups.
Dr Elia: I think that you should try to have a more homogeneous Dr W. Klepetko (Vienna, Austria): Where precisely did you group of patients, like breast cancer patients and lung cancer insert the catheter, and how did you make sure there was an equal patients, separately. That probably would help in understanding the distribution of the tetracycline within the thoracic cavity? Dr Yildirim: Before the procedure we tried to find the best place Dr Yildirim: Yes, you might be right.
by using serial thoracentesis, by puncture needle, and then we Dr G. Cardillo (Rome, Italy): Have you considered in your group inserted the catheter, and before the insertion, we prepared the of patients the condition of the lung before pleurodesis? I mean a free solution at the calculated dose and then instilled it.
lung i.e. a lung that is able to expand after thoracentesis, usually Rapid pleurodesis in symptomatic malignant pleural effusion
Erkan Yildirim, Koray Dural, Rasih Yazkan, Nurullah Zengin, Dilsad Yildirim, Nesimi This information is current as of July 14, 2009
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