The use of octreotide in the treatment of chylothorax following cardiothoracic surgery

Abstract

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was ‘Is octreotide (a long-acting somatostatin analogue) effective in patients with post-operative or traumatic chylothorax as a part of conservative management to reduce lymphorrhagia?’ Altogether 180 papers were found using the reported search, of which 20 represented the best evidence to answer the clinical question. One case was reported twice and therefore was excluded, leaving us with 19 papers. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Although rare, iatrogenic and traumatic chylothorax have been well described in the literature. At present, there have been no randomized controlled clinical trials on the use of octreotide in chylothorax. Sixteen of 19 papers found octreotide to be effective in the treatment of chylothorax. Octreotide was found to have no complementary effect in three reports. Two of the papers were retrospective studies: one a randomized controlled trial in canines, and the remainder were case reports and case series. The two retrospective studies showed a success rate of 87–90% in the use of octreotide as an adjunct to conservative management for the treatment of chylothorax and hence preventing the need for further surgery. Experimental study in canines has shown significant drain reduction and earlier fistula closure, although transferability of this result to human is difficult to interpret. Twelve case reports found octreotide effective in reduction of the volume and arrest of chylothorax. Most reported benefit in 2–3 days of administration of octreotide. The general consensus is for conservative management with octreotide to be instituted for 1 week before consideration of surgery, although some authors have advocated for a large volume chylothorax, especially after oesophageal surgery with no response to conservative management with octreotide, to be operated on sooner. We concluded that octreotide is effective in the management of moderate to large volume chylothorax.

INTRODUCTION

A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].

THREE-PART QUESTION

In [patients with a chylothorax after thoracic surgery] is [octreotide] compared with [limited dietary fat intake alone] effective in [treating chylothorax]?

CLINICAL SCENARIO

A 48-year old woman underwent left video-assisted thoracoscopic surgery (VATS) lower lobectomy. On postoperative Day 4, she developed milky coloured fluid in her chest drain that was sent off for biochemical analysis. A diagnosis of chylothorax was confirmed with the triglyceride level of drain fluid being 1.91 mmol. A medium chain triglyceride (MCT) diet was instituted. You believe that Octreotide will help reduce the chylothorax, however you turn to the literature and review the best evidence available.

SEARCH STRATEGY

Medline and EMBASE 1950 to August 2014 using OVID interface (chylothorax.mp OR chylothoraces.mp OR thoracic duct/OR thoracic duct injury.mp.) AND (sandostatin.mp OR somatostatin.mp OR octreotide.mp.).

Search limit: English language, age groups: Adult

SEARCH OUTCOME

A total of 180 papers were found using the reported search. From these, 19 papers were identified that provided the best evidence to answer the question. These are presented in Table 1.

RESULTS

Traumatic and iatrogenic chylothorax following cardiothoracic or oesophageal surgery has been well documented in the literature. However, due to the rarity of the condition, there has been no randomized controlled trial on the subject to date. In 1990, Ulibarri et al. [12] were the first to describe the successful use of somatostatin in an adult patient with chyle leak due to injury to thoracic duct following laryngectomy and lymphadenectomy.

The only trial available on the subject was an animal study. Markham et al. [3] conducted a randomized controlled trial in canines that showed a significant reduction in drain output on Day 2 of treatment with octreotide and earlier fistula closure. This experimental work showed efficacy of octreotide; however, considerable differences between canines and humans make the transferability of the result to clinical practice uncertain.

The benefits of octreotide in chylothorax following thoracic surgery were described in five separate reports [2, 4–7, 9, 14]. Bryant et al. [2] conducted a retrospective study with the largest number of patients to date (n = 41), with chylothorax following pulmonary resections and lymphadenectomy by means of thoracotomy and robotic approach. Success rate of treatment with octreotide was 90%. However, it was unclear whether the chylothorax was high or moderate volume in these cases. Gomez-Caro et al. [6] described 4 patients with chylothorax following thoracic surgery (lobectomies, VATS procedure and exploratory thoracotomy and thoracic duct repair). The author demonstrated remarkable drain reduction of 85–91% upon administration of octreotide when total parenteral nutrition (TPN) and nil by mouth (NBM) alone failed to change the drain output. Drain removal in these cases ranged between 2 and 5 days after commencement of octreotide. Sharkey et al. [9] shared a similar experience in 2 patients with significant drain output reduction after 3 days of treatment with octreotide, avoiding surgery. In both patients, serum albumin showed improvement as chylothorax resolved. Mafe et al. [5] described a successful conservative management of moderate volume chylothorax after thymectomy via median sternotomy. Findikcioglu et al. [7] looked at a patient who developed chylothorax following extrapleural pneumonectomy who had been successfully treated with octreotide; however, the author used MCT diet instead of TPN and complete bowel rest, which may explain the later drainage cessation compared with other cases (Day 10). Mikroulis et al. [8] on the other hand found a significant reduction of chylothorax with TPN and NBM alone, but no change was observed when octreotide was given in a patient following pneumonectomy and lymphadenectomy. There was no change to serum albumin level on octreotide, which improved only with MCT diet. Demos et al. [14] commented on his experience of using octreotide in 5 patients with an 80% success rate. The groups of patients included were a mixture of traumatic and spontaneous chylothorax: post-lobectomies, lymphoma, pulmonary lymphangiomatosis and end-stage post-hepatitic cirrhosis. The failure in 1 case was thought to be due to the liver failure whereby the chylothorax resolved once liver disease recovered.

The successful treatment of chylothorax following cardiac surgery has been described in six case reports and literature reviews. Barbetakis et al. [18] described a case of chylothorax following coronary artery bypass grafting (CABG) with left internal mammary artery (LIMA) to left anterior descending artery injury to thoracic duct during the harvest of LIMA, successfully managed with octreotide along with TPN and NBM. The drain output showed significant reduction by >80% and removal of drain at Day 8. The author reviewed 24 other cases of chylothorax after CABG, with 2 patients receiving octreotide; however, the outcome was not discussed. Kelly et al. [15] shared a successful experience of the use of octreotide in chylothorax following CABG whereby the drain output decreased by 60% in 24 h and complete resolution was achieved in only 2 days. Gabbieri et al. [16] and Kilic et al. [17] reported similar successful experience in moderate volume chylothorax following CABG. Authors recommended octreotide as an adjunct early in the conservative management following cardiac surgery.

Chylothorax in oesophagectomy is more common than in cardiothoracic surgery due to the anatomy and the nature of the surgery. Fujita et al. [11] conducted a retrospective study in a single centre, comparing the use of octreotide along with TPN and NBM against TPN and NBM only for patients with chylothorax following oesphagectomy and lymphadenectomy. The group receiving octreotide has significantly more successful conservative management compared with the group receiving TPN and bowel rest only. Daily drain output also significantly decreased in the octreotide group, with mean interval for drain removal of 3–4 days after treatment with octreotide. Okumura et al. [12], however, described a case of failure of treatment in a similar setting. Although reduction of drainage was seen with the administration of octreotide in this case (3–2 l/day), it was not adequate to safely continue with conservative management. Thoracic duct ligation was undertaken and octreotide was continued afterwards with good result. Failure in this case is probably due to a high-volume chylothorax (3 l/day). Disruption in the main thoracic duct itself in oesophagectomies tends to produce a high-output chylothorax as opposed to pulmonary resections. The general consensus is to conservatively manage these patients with TPN, bowel rest and octreotide for only 48 h and if there is no response, reoperation is recommended [2, 11, 12].

Srikumar et al. [14] described a successful treatment with octreotide in a patient with bilateral chylothorax following radical neck dissection, although the volume of chylothorax was not stated in this case. The author recommended re-exploration of the neck along with the use of octreotide to avoid thoracic intervention, although in this case re-exploration of the neck did not influence the outcome as no thoracic duct injury was found.

Fujita et al. [11] found that a high-output chylothorax (>1 l/day), persisting for 2 days after 48 h treatment with octreotide is the predicting factor for failure of treatment with octreotide. This is supported by the findings of Okumura et al. [12] whereby octreotide does reduce the drainage of 2–3 l/day chylothorax, but did not cause resolution of chylothorax.

CLINICAL BOTTOM LINE

Octreotide along with TPN and bowel rest is effective in reducing volume of drainage in cases of chylothorax caused by injury to thoracic duct or its branches. In most reports, the benefit is seen within 2–3 days of treatment of octreotide. The general consensus is for conservative management with octreotide to be instituted for 1 week before consideration of surgery. Some authors have advocated for large volume chylothorax to be operated on sooner, especially after oesophageal surgery, with no response to conservative management with octreotide.

Conflict of interest: none declared.

REFERENCES