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Octreotide in the management of chyle leaks after head and neck surgery: a systematic review of cohort studies

Published online by Cambridge University Press:  21 July 2026

Nimeshi Jayakody Open the ORCID record for Nimeshi Jayakody [Opens in a new window] ,
Phillip Brown ,
Callum Findlay  and
Nimesh N. Patel
Nimeshi Jayakody*
Affiliation:
University Hospital Southampton NHS Foundation Trust, UK
Phillip Brown
Affiliation:
University Hospital Southampton NHS Foundation Trust, UK
Callum Findlay
Affiliation:
University of Southampton School of Clinical and Experimental Sciences, UK Department of Otolaryngology, University Hospital Southampton NHS Foundation Trust, UK
Nimesh N. Patel
Affiliation:
Department of Otolaryngology, University Hospital Southampton NHS Foundation Trust, UK
*
Corresponding author: Nimeshi Jayakody; Email: nimeshi01@hotmail.co.uk
Rights & Permissions [Opens in a new window]

Abstract

Objective

To review the literature to understand the efficacy of octreotide in managing post head and neck surgery chyle leaks.

Method

Literature from January 1980 to May 2025 was systematically reviewed using PubMed, Medline, Embase and Cochrane databases. Exclusion criteria involved non-English papers, conference abstracts and case reports with fewer than five cases.

Results

Six retrospective case series, totalling 107 patients, met inclusion criteria. Median chyle leak resolution time was 5.5 days (range, 2–24 days), with an in-patient stay of 7 to 11.8 days. Surgery to limit chyle leak was performed on 15.9 per cent of patients (17 of 107 cases) therefore 84.1 per cent were successfully treated with octreotide.

Conclusion

This systematic review suggests that octreotide is effective in managing low- and high-output chyle leaks post head and neck surgery and should be considered at day one of diagnosis. The dose recommendation is 100 μg three times a day. Surgery should be reserved for those who do not respond to octreotide and other conservative measures.

Keywords

chyleneck dissectionoctreotide

Information

Type
Review Article
Information
The Journal of Laryngology & Otology , First View , pp. 1 - 6
Copyright
© The Author(s), 2026. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED.

Introduction

A chyle leak is a serious and potentially harmful complication following head and neck surgery.Reference Moola, Munn, Tufanaru, Aromataris, Sears and Sfetcu1 This complication arises as a result of the major lymphatic ducts—the thoracic duct and the right lymphatic duct—connecting to the venous system in the neck, rendering them susceptible to injury during neck surgery.Reference Moola, Munn, Tufanaru, Aromataris, Sears and Sfetcu1–Reference Lucente, Diktaban, Lawson and Biller3 The incidence of iatrogenic injury during head and neck surgery is reported to be between 1 per cent and 2.5 per cent.Reference Moola, Munn, Tufanaru, Aromataris, Sears and Sfetcu1, Reference Lucente, Diktaban, Lawson and Biller3 These ducts can join the left internal jugular vein or the right subclavian vein, or exhibit variations, increasing the likelihood of iatrogenic injury, especially during left-sided neck surgery.Reference Moola, Munn, Tufanaru, Aromataris, Sears and Sfetcu1, Reference Jain, Singh, Singhal, Sharma and Grover4–Reference Phang, Bowman, Phillips and Windsor6 The lymphatic ducts play a crucial role in fluid balance and fat transport, notably transporting chylomicrons containing long-chain fatty acids absorbed from the intestinal lymphatic system.Reference Lucente, Diktaban, Lawson and Biller3, Reference Jain, Singh, Singhal, Sharma and Grover4 Treatment strategies are intricately designed around these fundamental functions.Reference Moola, Munn, Tufanaru, Aromataris, Sears and Sfetcu1

Diagnosis and prompt treatment of chyle leak are imperative for two reasons. First, it disrupts fluid balance, electrolytes and fat metabolism, potentially leading to malnourishment, electrolyte imbalances and hypovolemia.Reference Moola, Munn, Tufanaru, Aromataris, Sears and Sfetcu1, Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference De Gier, Balm, Bruning, Gregor and Hilgers7 Second, chyle hinders wound repair by creating a barrier to healing, increasing the risk of infection and affecting the immune response by depleting lymphocytes.Reference Lucente, Diktaban, Lawson and Biller3, Reference De Gier, Balm, Bruning, Gregor and Hilgers7 Chyle typically has a milky white appearance, and the diagnosis is confirmed by analysing the biochemical composition of triglycerides and proteins in the leaking fluid.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9

The management of chyle leaks depends on whether injury to the thoracic duct is identified immediately or post-operatively.Reference Lucente, Diktaban, Lawson and Biller3, Reference Seow, Murray and McKee10 During surgery, options include ligating the thoracic duct proximally to the injury using clips or sutures, applying topical substances like tetracycline or fibrin glue, or employing muscle flaps such as sternocleidomastoid, anterior scalene and pectoralis major to cover the surgical area.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Seow, Murray and McKee10, Reference Delaney, Shi, Shokrani and Sinha11

The protocols for managing chyle leaks post-operatively are diverse, including conservative, surgical and medical options.Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Smoke and DeLegge12 Until now, the evidence for the use of octreotide in head and neck chyle leaks has been weak.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4 Octreotide is thought to decrease chyle production by impacting the gastrointestinal system, although the exact mechanism remains unclear.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Seow, Murray and McKee10 The objective of this research was to evaluate the efficacy of octreotide as a medical treatment for chyle leaks and its impact on resolving the leaks through a comprehensive analysis of available evidence.

Methods

Search strategy

A comprehensive online literature search was conducted using Medical Subject Headings (MeSH terms). The search encompassed databases including Medline, Embase, PubMed and Cochrane, covering publications from January 1980 to May 2025. To ensure all relevant papers on chyle leaks were identified, an extensive search employing various MeSH terms was carried out. The search strategy included ‘chyl*’, ‘chyle’, ‘lymph leak’, ‘head and neck surgery’, ‘dissection’ and ‘octreotide/somatostatin analogue’.

Articles reporting animal or experimental studies, conference articles, paediatric cases, individual case reports, case series reporting fewer than five cases and studies which did not trial octreotide were excluded. Non-English language papers and articles where full text was not available free of charge were also excluded.

Articles were screened by title, abstract and subsequently full text. Duplicate papers were excluded. References in included articles were reviewed to ensure all relevant articles were identified and screened.

Data retrieval and quality assessment

The literature search was conducted by a single researcher (NJ), and cases of uncertainty were reviewed independently by second and third researchers (PB and NP). Two researchers (PB and NP) assessed each article using the Joanna Briggs Institute Critical Appraisal tool for case series, rating them on a scale of 1 to 10.Reference Munn, Barker, Moola, Tufanaru, Stern and McArthur13 This tool evaluates quality of case series through adherence to inclusion criteria, methodological standards, reporting of participant demographics, clinical details and outcome information.Reference Munn, Barker, Moola, Tufanaru, Stern and McArthur13

Data extraction was performed by NJ. The extracted data included patient count, patient demographics, surgical procedures, chyle leak diagnostic techniques, chyle leak volume, octreotide use, nutritional treatment regimen and further surgical interventions. Primary outcome measures from the studies included time for chyle leak resolution and the necessity for further surgical intervention. Length of hospital in-patient admission was also evaluated. This information was recorded in a structured pro-forma and independently reviewed by PB and NP.

Data analysis

Given the divergent methodologies, available data and heterogeneity across the studies, a meta-analysis was infeasible. Descriptive statistical calculations were performed using IBM SPSS version 25 (New York, Unites States of America). Visual representations were generated utilising Microsoft Excel 365 suite 2022 Washington, United States of America).

Results

A total of 518 articles were identified through the online literature search. After removing duplicates and reviewing titles, 60 articles were selected for abstract review. Thirty-three articles underwent full-text review. In cases where publications reported data from the same cohort or follow-up studies, preference was given to the most recent publication. On applying inclusion and exclusion criteria, a total of six articles were ultimately selected for inclusion in this systematic review.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 The article review process can be seen in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist diagram provided in Figure 1.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist flow diagram showing the strategy for systematic review.

The systematic review process from identification to inclusion of studies. See long description.
Figure 1 Long description

The systematic review process has three main sections: Identification, Screening and Included. Identification: Records identified from databases (n = 601) and registers (n = 11), totaling 612. Records removed before screening: Duplicate records removed (n = 94). Screening: Records screened (n = 518). Records excluded (n = 458). Reports sought for retrieval (n = 60). Reports not retrieved (n = 27). Reports assessed for eligibility (n = 33). Reports excluded (n = 27): Case series with less than 5 cases (n = 8). Does not meet inclusion/exclusion criteria (n = 19). Included: Studies included in review (n = 6).

All six studies included in this analysis were case series.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 The quality scores for these publications ranged from 5 out of 10 to 9 out of 10, with an average score of 6 out of 10.Reference Munn, Barker, Moola, Tufanaru, Stern and McArthur13 Methodologies employed across these studies were inconsistent. A summary of the included studies is shown in Table 1.

Table 1.

Baseline characteristics of publications included in the analysis (n/a-not available)

Six publications span South Korea, India, Hong Kong, and the USA, with quality scores from 5 to 9 and high output drain thresholds from over 200 to over 1000 milliliters per 24 hours. See long description.
Table 1 Long description

Columns list publication, country, patients, patient and study characteristics, Joanna Briggs Institute quality score out of 10, definition of drain output, and comments. Ahn et al. 2015 from South Korea reports 22 patients and 472 in parentheses, left or right modified or radical neck dissection, quality score 9, and high output defined as more than 1000 milliliters per 24 hours; comments note octreotide was given only to selected high output patients, 4. Jain et al. 2015 from India reports 19 patients with n slash a in parentheses, left sided modified or radical neck dissection, quality score 6, and high output defined as more than 500 milliliters per 24 hours, with no comment. Chan et al. 2017 from Hong Kong reports 10 patients and 438 in parentheses, left or right modified or radical neck dissection, quality score 5, and high output defined as more than 200 milliliters per 24 hours, with no comment. Swanson et al. 2015 from the USA reports 12 patients with n slash a in parentheses, neck dissection with thyroidectomy and parathyroidectomy, quality score 6, and drain output definition listed as n slash a, with no comment. Gupta et al. 2021 from India reports 16 patients and 390 in parentheses, bilateral or left selective neck dissection, quality score 9, and high output defined as more than 500 milliliters per 24 hours, with a dash in comments. Strama et al. 2024 from the USA reports 28 patients with n slash a in parentheses, neck dissection, quality score 7, and drain output defined as more than 1000 milliliters per 24 hours; comments note only the otolaryngology subgroup was selected.

ND = neck dissection.

Most studies, primarily because of the nature of the disease pathology, were retrospective case studies. One publication was conducted prospectively.Reference Jain, Singh, Singhal, Sharma and Grover4 The number of participants ranged from 12 to 28, with diverse populations included. Two studies were performed in IndiaReference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4 and two in the USA,Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 while the remaining studies were from Hong KongReference Chan, Wong, Ng, van Hasselt and Vlantis9 and South Korea.Reference Ahn, Sohn and Jeong8

The total number of patients reported across the six studies was greater than 1300, but only three of six studies reported the total study population.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9 Across all six studies there were 107 reported chyle leaks with a median occurrence range of 2.1 per cent to 4.7 per cent. Most studies described baseline characteristics of the patient population who developed a chyle leak.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9 Of those that describe the operative statistics, 57 patients (72.2 per cent) had left-sided neck dissections, 10 (12.7 per cent) had bilateral dissections, 10 (12.7 per cent) had right-sided dissections and 2 (2.5 per cent) had central neck dissections (1 paper did not give the operative breakdownReference Strama, Rice, Ruff, Carter, Ernst and Kuebel15). Out of these 79 patients, 58 (73.4 per cent) were noted to have nodal disease. Literature suggests that the risk factors for chyle leak are men over the age of 50 years, left-sided modified radical neck dissections, the presence of metastatic lymph nodes and previous irradiation.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15

Diagnosis of chyle leak was mostly clinical, based on the appearance of the leaking fluid, and occasionally drain triglyceride or chylomicron concentration was used to confirm the diagnosis or in cases where the diagnosis was uncertain.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8 Definitions of high-output chyle leaks varied among publications, with suggested volumes ranging from 200 to 1000 ml per 24 h.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 The majority of publications suggested a 500 ml/24 h threshold.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8 In most cases, those who failed to respond to octreotide experienced high-output chyle leaks, and these leaks were predominantly detected three to five days post-operatively.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15

All six studies included nutritional interventions.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 These interventions varied and included total parenteral nutrition, medium-chain triglyceride diets, low-fat diets and no-fat diets.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 Most studies employed a combination of nutritional management methods together with octreotide.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15

The initiation of octreotide treatment varied among studies, with most commencing treatment between days 3 and 10Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 post-diagnosis, whilst others started immediately post-operatively if the chyle leak was identified intra-operatively or if a trial of nutritional management was not successful.Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 The duration of octreotide treatment also differed, with some studies prescribing a fixed 5- or 7-day course,Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 while others adjusted based on output (ranging from 2 to 20 days).Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 See Table 2 for a summary of primary and secondary outcomes.

Table 2.

Primary outcomes (length of time for resolution of chyle leak in patients who had octreotide) and secondary outcomes of the study (length of in-patient stay, percentage of patients who had surgical management). (MCT = Medium Chain Triglycerides, TPN = Total Parental Nutrition, n/a = Not available.)

Median time to resolve chyle leaks with octreotide ranged from 4 to 13.8 days across studies that reported it. See long description.
Table 2 Long description

Publications are compared by number of chyle leaks, occurrence percent, treatment, median days to resolution, median days of in patient stay, number who underwent surgery, and mortality. Ahn et al. 2015 reported 22 chyle leaks out of 472, 4.7 percent, treated with octreotide and total parenteral nutrition, with resolution and in patient stay not reported; surgery was 4 patients, 18.2 percent, and mortality was 0. Jain et al. 2015 reported 19 chyle leaks with total not reported and occurrence percent not reported, treated with octreotide and middle chain triglycerides; resolution was 13.8 days with a range of 11 to 17, in patient stay was 11.8 days with a range of 9 to 15, surgery was 0, and mortality was 0. Chan et al. 2017 reported 10 chyle leaks out of 438, 2.3 percent, treated with octreotide, middle chain triglycerides, and total parenteral nutrition; resolution was 11.9 days with a range of 3 to 24, in patient stay not reported, surgery was 2 patients, 20.0 percent, and mortality was 1 patient, 10.0 percent. Swanson et al. 2015 reported 12 chyle leaks with total not reported and occurrence percent not reported, treated with octreotide, middle chain triglycerides, and total parenteral nutrition; resolution was 5.5 days with a range of 2 to 11, in patient stay was 8.7 days with a range of 3 to 18, surgery was 0, and mortality was 0. Gupta et al. 2021 reported 16 chyle leaks out of 390, 4.1 percent, treated with octreotide and total parenteral nutrition; resolution was 5.2 days with a range of 3 to 10, in patient stay was 12.2 days with a range of 9 to 18, surgery was 1 patient, 6.3 percent, and mortality was 0. Strama et al. 2024 reported 28 chyle leaks with total not reported and occurrence percent not reported, treated with octreotide, middle chain triglycerides, and total parenteral nutrition; resolution was 4 days with a range of 2 to 5.3, in patient stay was 7 days with a range of 5 to 9.5, surgery was 10 patients, 35.7 percent, and mortality was 0.

The median time for chyle leak resolution was 5.5 days (range, 2–24 days).Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 The range of length of in-patient stay, calculated from 4 studies, was 7–11.8 days.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 Out of all the chyle leaks, 17 patients required surgery, with the majority being high-output cases, representing a range of 6.3 per cent to 35.7 per cent needing surgical correction,Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 but it should be noted that this is skewed by 1 study that had an higher than average number of leaks.Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 This indicates that 84.1 per cent of patients successfully resolved their condition with octreotide alongside nutritional management.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 One reported mortality was attributed to sepsis, cellulitis and multiorgan failure.Reference Chan, Wong, Ng, van Hasselt and Vlantis9

Discussion

Octreotide was first successfully used by Ulíbarri et al. in 1990 to treat chyle leaks from the thoracic duct.Reference Ulíbarri, Sanz, Fuentes, Mancha, Aramendia and Sánchez16 Its application in managing chyle leaks related to head and neck surgery is increasingly recognised as a viable medical treatment option.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 While previous systematic reviews have largely relied on case reports and small case series,Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Magoo, Bhate, Kakodkar, Gajul and Mastud17 this article aims to present an up-to-date review utilising higher-quality, larger cohort studies to evaluate the effectiveness of octreotide.

Risk factors, diagnosis and other treatment modalities

Several publications in this review identify metastatic neck nodes as a significant risk factor for chyle leaks.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference De Gier, Balm, Bruning, Gregor and Hilgers7 Other notable risk factors include squamous cell carcinoma, prior radiotherapy, age over 50 years and male gender, the latter two being associated with the higher incidence of head and neck cancer in these demographics.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Seow, Murray and McKee10, Reference Crumley and Smith18, Reference Roh, Park and Park19

Diagnostically, the characteristic ‘milky white’ appearance of chyle is commonly described and measuring triglycerides (>100 mg/dl) or detecting chylomicrons is regarded as the most reliable laboratory test.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 Low-output chyle leaks are typically defined by a drainage output of 500 ml or less over 24 h.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4

Conservative management is widely recommended as the first-line treatment, including pressure dressings, suction drainage, bed rest, laxatives to minimise thoracic pressure and low-fat and/or no-fat or medium-chain triglyceride diets.Reference Smoke and DeLegge12, Reference Izzard, Crowder and Southwell20–Reference Homer, Winter, Abbey, Aga, Agrawal and Ap Dafydd22 Octreotide is often employed alongside these measures, particularly for low-output leaks.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2 When conservative measures fail, total parenteral nutrition may be considered, although its use is tempered by associated risks such as infection and flap necrosis.Reference Smoke and DeLegge12, Reference Homer, Winter, Abbey, Aga, Agrawal and Ap Dafydd22, Reference Meyer, McLeod and Gallagher23 For high-output leaks (>1000 ml/24 h), prompt surgical intervention is advised to reduce hospital stays and morbidity.Reference Ahn, Sohn and Jeong8 Following resolution, a gradual reintroduction of a regular diet over two to four weeks is typically recommended.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2

Intra-operative and post-operative techniques have evolved to address refractory leaks. Sclerosing agents like OK-432 or tetracycline have shown success in managing thoracic duct injuries.Reference Lorenz, Abuazab, Sekulla, Nguyen-Thanh, Brauckhoff and Dralle24, Reference Roh, Yoon and Park25 Muscle flaps, such as the pectoralis major, scalenus anterior or sternocleidomastoid, are frequently used for repair.Reference De Gier, Balm, Bruning, Gregor and Hilgers7 Intra-operative ligation with non-absorbable sutures (e.g. Prolene) is another effective strategy.Reference De Gier, Balm, Bruning, Gregor and Hilgers7, Reference Smoke and DeLegge12 Additionally, advances in interventional radiology, such as lymphography-guided embolisation, have demonstrated efficacy in treating iatrogenic or traumatic thoracic duct injuries, offering a minimally invasive alternative to surgery.Reference Kawasaki, Sugimoto, Fujii, Miyamoto, Okada and Yamaguchi26

Octreotide as a treatment modality

The therapeutic use of octreotide, a somatostatin analogue, was first reported in 1973.Reference Brazeau, Vale, Burgus, Ling, Butcher and Rivier27 Subsequent trials in the 1980s demonstrated its efficacy in reducing thoracic chyle output in dogs.Reference Delaney, Shi, Shokrani and Sinha11 This discovery eventually led to its introduction in clinical medicine, initially as an adjunct to conservative therapy for a patient undergoing supraglottic laryngectomy, as reported by Ulíbarri et al.Reference Ulíbarri, Sanz, Fuentes, Mancha, Aramendia and Sánchez16

Somatostatin, a naturally occurring paracrine neurohormonal substance, exhibits diverse physiological activities, including inhibition of the secretion of hormones such as gastrin, growth hormone and thyroid-stimulating hormone.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Magoo, Bhate, Kakodkar, Gajul and Mastud28 Although the precise mechanism of action of octreotide remains incompletely understood, it is believed to reduce pancreatic and gastrointestinal secretions, hepatic venous pressure and splanchnic blood flow.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Magoo, Bhate, Kakodkar, Gajul and Mastud28 Additionally, it may constrict lymphatic ducts, which is considered a potential mechanism in mitigating chyle leaks.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Magoo, Bhate, Kakodkar, Gajul and Mastud28

Dosage regimens for octreotide in the treatment of chyle leaks vary, with studies reporting doses ranging from 50 to 200 μg administered up to 3 times daily.Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 Most commonly, a dosage of 100 μg thrice daily has been used. Chan et al. increased the dose to 200 μg thrice daily in cases of non-response.Reference Chan, Wong, Ng, van Hasselt and Vlantis9 Similarly, Swanson et al. utilised varying dosages from 50 μg twice daily to 150 μg four times daily, with 100 μg thrice daily being the most frequently employed regimen.Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 Strama et al did a weight-related dosage with different routes of administrationReference Strama, Rice, Ruff, Carter, Ernst and Kuebel15.

Timing of octreotide initiation varied among studies. Jain et al. started octreotide between days 5 and 10 after conservative measures were exhausted, using it for 5 days in low-output leaks and 7 days in high-output leaks.Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 In contrast, Gupta et al. initiated treatment on the first day of a chyle leak and continued until two days after the leak resolved.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2 Ahn et al. reserved octreotide for high-output leaks (>1000 ml/24 h) after conservative measures failed, although the exact timing of initiation was unclear.Reference Ahn, Sohn and Jeong8 Chan et al., Swanson et al. and Strama et al. began octreotide alongside conservative therapy on the first day for both low- and high-output leaksReference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15. The overall consensus suggests initiating octreotide at diagnosis for both low- and high-output leaks and continuing treatment until resolution.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15

Of the six studies reviewed, four reported cases requiring surgical re-exploration because of persistent high-output chyle leaks.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 Ahn et al. recommended surgery for patients with unresolved high-output leaks after four days of octreotide therapy.Reference Ahn, Sohn and Jeong8 Strama et al. and Gupta et al. also advocated surgical intervention for persistently high output, although they did not specify a definitive timeframeReference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15. Chan et al. proposed considering surgery if no improvement was observed after five days, emphasising the importance of individualised assessment based on each patient’s response to conservative and medical therapies, as well as their hemodynamic status.Reference Chan, Wong, Ng, van Hasselt and Vlantis9

All studies administered octreotide subcutaneously, except Chan et al., who opted for intravenous administration for ease and safety,Reference Chan, Wong, Ng, van Hasselt and Vlantis9 and Strama et al., who used different types of administration (intravenous and subcutaneous)Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15. Currently, the cost of octreotide is approximately £32 for five 100-μg ampoules.29 While none of the studies explicitly assessed cost-effectiveness, many implied that reduced need for surgical intervention and shorter hospital stays could make octreotide a cost-efficient treatment option.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4

Reported side effects of octreotide include abdominal pain, steatorrhea, indigestion, nausea, vomiting, glucose dysregulation, hepatic dysfunction, allergic reactions, intestinal bleeding and pulmonary embolism.Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Magoo, Bhate, Kakodkar, Gajul and Mastud28, Reference Markham, Glover, Welsh, Lucas and Bendick30 Additionally, an increased risk of gallstone formation has been noted. Gupta et al. reported nausea, abdominal discomfort and diarrhoea as side effects,Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2 while Swanson et al. observed nausea and dizziness.Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 None of these side effects necessitated cessation of therapy. However, a death due to gastrointestinal bleeding was reported by Chan et al., although it was attributed to the overall complications of the chyle leak rather than octreotide therapy itself.Reference Chan, Wong, Ng, van Hasselt and Vlantis9

Limitations

The primary constraint observed in the majority of the utilised studies is their reliance on level three evidence, case series.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 In an effort to enhance reliability, publications featuring more than five patients were included; nevertheless, discrepancies persist because of the inherent characteristics of the studies, such as potential selection bias in data collection.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15 Given the small sample sizes, it becomes challenging to assess the efficacy of treatment strategies, thereby complicating the formulation of recommendations.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Ahn, Sohn and Jeong8, Reference Chan, Wong, Ng, van Hasselt and Vlantis9, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14, Reference Strama, Rice, Ruff, Carter, Ernst and Kuebel15

Some of the studies lack comprehensive details regarding patient baseline characteristics, diagnostic methods and terminology definitions, and exhibit heterogeneity in terms of geographical location, types of surgery and variations in clinical decisions at different stages of the patient’s journey, rendering interpretation of the dataset challenging.Reference Jain, Singh, Singhal, Sharma and Grover4, Reference Swanson, Hudson, Bhandari, Sinha, Maceri and Kokot14 In most studies, when an intra-operative chyle leak was identified, surgeons undertook repairs, which could have led to reporting bias.Reference Gupta, Dwivedi, Chugh, Sahu, Gupta and Basu2, Reference Ahn, Sohn and Jeong8

Future directions

Additional high-level evidence is required to establish robust recommendations for addressing chyle leaks. It is suggested that certain pre-operative measures, such as administering fat loading or using cyano dye, may improve intra-operative diagnosis of chyle leaks.Reference Kawasaki, Sugimoto, Fujii, Miyamoto, Okada and Yamaguchi26 Medical management with longer-acting somatostatin analogues like lanreotide and the use of sclerosing agents also show potential but require further research to determine their effectiveness in treating chyle leaks and superiority over octreotide.Reference Lorenz, Abuazab, Sekulla, Nguyen-Thanh, Brauckhoff and Dralle24 To gain a better understanding of this intricate condition, further investigation and more comprehensive characterisation of patient groups, along with standardised treatment protocols in prospective studies, are essential.

  • • This study presents the most up-to-date systematic review of octreotide for post head and neck surgery chyle leaks, incorporating cohort-level evidence published up to May 2025 and expanding substantially on previous reviews that were limited mainly to case reports and small series

  • • The largest pooled clinical dataset to date (107 patients) is reported, offering more reliable estimates of treatment success, time to resolution, in-patient stay and rates of conversion to surgical management

  • • It is demonstrated that octreotide, when combined with nutritional management, successfully resolves over 84 per cent of chyle leaks, supporting its role as first-line medical therapy and significantly reducing the need for surgical re-exploration

  • • The early initiation of octreotide from the day of diagnosis for both low- and high-output chyle leaks is supported, rather than reserving medical therapy only after failure of conservative measures

  • • A dosing strategy of 100 μg subcutaneously three times daily is suggested, providing clinicians with a clear and standardised treatment framework

Conclusion

We recommend the use of octreotide for all chyle leaks (low or high output) together with other conservative measures and continuing until the output has resolved. The dosage recommended is 100 μg three times a day. Surgery should be considered in patients who continue to have high output despite the above treatment and should be determined on a case-by-case basis.

Competing interests

None declared.

Acknowledgements

AI was used for editing this publication only. It was not used for writing, referencing or any other purpose.

Footnotes

Nimeshi Jayakody takes responsibility for the integrity of the content of the paper

References

Moola, S, Munn, Z, Tufanaru, C, Aromataris, E, Sears, K, Sfetcu, R et al. Systematic reviews of etiology and risk. In: Joanna Briggs Institute Reviewer’s Manual. Adelaide: Joanna Briggs Institute, 2017; 2019–205Google Scholar
Gupta, V, Dwivedi, G, Chugh, R, Sahu, PK, Gupta, DK, Basu, A et al. Role of octreotide in conservative management of chyle leak post neck dissection in cases of head neck cancer: a retrospective analysis. Indian J Otolaryngol Head Neck Surg 2021;73:1–9Google Scholar
Lucente, FE, Diktaban, T, Lawson, W, Biller, HF. Chyle fistula management. Otolaryngol Head Neck Surg 1981;89:575–810.1177/019459988108900413CrossRefGoogle ScholarPubMed
Jain, A, Singh, SN, Singhal, P, Sharma, MP, Grover, M. A prospective study on the role of octreotide in management of chyle fistula neck. Laryngoscope 2015;125:1624–710.1002/lary.25171CrossRefGoogle ScholarPubMed
Langford, RJ, Daudia, AT, Malins, TJ. A morphological study of the thoracic duct at the jugulo-subclavian junction. J Craniomaxillofac Surg 1999;27:100–410.1016/S1010-5182(99)80021-3CrossRefGoogle ScholarPubMed
Phang, K, Bowman, M, Phillips, A, Windsor, J. Review of thoracic duct anatomical variations and clinical implications. Clin Anat 2014;27:637–4410.1002/ca.22337CrossRefGoogle ScholarPubMed
De Gier, HHW, Balm, AJM, Bruning, PF, Gregor, RT, Hilgers, FJM. Systematic approach to the treatment of chylous leakage after neck dissection. Head Neck 1996;18:347–5110.1002/(SICI)1097-0347(199607/08)18:4<347::AID-HED6>3.0.CO;2-Y3.0.CO;2-Y>CrossRefGoogle Scholar
Ahn, D, Sohn, JH, Jeong, JY. Chyle fistula after neck dissection: an 8-year, single-center, prospective study of incidence, clinical features, and treatment. Ann Surg Oncol 2015;22:1000–610.1245/s10434-015-4822-7CrossRefGoogle ScholarPubMed
Chan, JYK, Wong, EWY, Ng, SK, van Hasselt, CA, Vlantis, AC. Conservative management of postoperative chylous fistula with octreotide and peripheral total parenteral nutrition. Ear Nose Throat J 2017;96:264–710.1177/014556131709600720CrossRefGoogle ScholarPubMed
Seow, C, Murray, L, McKee, RF. Surgical pathology is a predictor of outcome in post-operative lymph leakage. Int J Surg 2010;8:636–810.1016/j.ijsu.2010.07.297CrossRefGoogle ScholarPubMed
Delaney, SW, Shi, H, Shokrani, A, Sinha, UK. Management of chyle leak after head and neck surgery: review of current treatment strategies. Int J Otolaryngol 2017;2017:1–610.1155/2017/8362874CrossRefGoogle ScholarPubMed
Smoke, A, DeLegge, MH. Chyle leaks: consensus on management? Nutr Clin Pract 2008;23:529–3210.1177/0884533608323424CrossRefGoogle ScholarPubMed
Munn, Z, Barker, TH, Moola, S, Tufanaru, C, Stern, C, McArthur, A et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. JBI Evid Synth 2020;18:2127–33Google Scholar
Swanson, MS, Hudson, RL, Bhandari, N, Sinha, UK, Maceri, DR, Kokot, N. Use of octreotide for the management of chyle fistula following neck dissection. JAMA Otolaryngol Head Neck Surg 2015;141:723–710.1001/jamaoto.2015.1176CrossRefGoogle ScholarPubMed
Strama, KL, Rice, TD, Ruff, JP, Carter, KE, Ernst, NE, Kuebel, DJ et al. Octreotide dosing in the medical management of chyle leak following otolaryngologic, thoracic, and trauma surgery: a 9-year evaluation. J Pharm Pract 2024;37:93–910.1177/08971900221125831CrossRefGoogle Scholar
Ulíbarri, J, Sanz, Y, Fuentes, C, Mancha, A, Aramendia, M, Sánchez, S. Reduction of lymphorrhagia from ruptured thoracic duct by somatostatin. Lancet 1990;336:25810.1016/0140-6736(90)91793-ACrossRefGoogle ScholarPubMed
Magoo, S, Bhate, K, Kakodkar, P, Gajul, M, Mastud, S. Effect of octreotide in stopping post-surgical chyle leak in neck dissection – a systematic review. J Oral Biol Craniofac Res 2022;12:737–4110.1016/j.jobcr.2022.08.018CrossRefGoogle ScholarPubMed
Crumley, RL, Smith, JD. Postoperative chylous fistula prevention and management. Laryngoscope 1976;86:805–1310.1288/00005537-197606000-00008CrossRefGoogle ScholarPubMed
Roh, JL, Park, JY, Park, CI. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann Surg 2007;245:604–1010.1097/01.sla.0000250451.59685.67CrossRefGoogle ScholarPubMed
Izzard, ME, Crowder, VL, Southwell, KE. The use of Monogen in the conservative management of chylous fistula. Otolaryngol Head Neck Surg 2007;136:S50–310.1016/j.otohns.2006.11.017CrossRefGoogle ScholarPubMed
Hong, X, Wang, X. Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol 2012;34:655–6910.1007/s00281-012-0323-yCrossRefGoogle ScholarPubMed
Homer, JJ, Winter, SC, Abbey, EC, Aga, H, Agrawal, R, Ap Dafydd, D et al. Head and neck cancer: United Kingdom national multidisciplinary guidelines. J Laryngol Otol 2024;138(S1):S1–224Google ScholarPubMed
Meyer, CD, McLeod, IK, Gallagher, DJ. Conservative management of an intraoperative chyle leak: a case report and literature review. Mil Med 2016;181 e1180–410.7205/MILMED-D-15-00240CrossRefGoogle Scholar
Lorenz, K, Abuazab, M, Sekulla, C, Nguyen-Thanh, P, Brauckhoff, M, Dralle, H. Management of lymph fistulas in thyroid surgery. Langenbecks Arch Surg 2010;395:911–1710.1007/s00423-010-0686-2CrossRefGoogle ScholarPubMed
Roh, JL, Yoon, YH, Park, CI. Chyle leakage in patients undergoing thyroidectomy plus central neck dissection for differentiated papillary thyroid carcinoma. Ann Surg Oncol 2008;15:2576–8010.1245/s10434-008-0017-9CrossRefGoogle ScholarPubMed
Kawasaki, R, Sugimoto, K, Fujii, M, Miyamoto, N, Okada, T, Yamaguchi, M et al. Therapeutic effectiveness of diagnostic lymphangiography for refractory postoperative chylothorax and chylous ascites: correlation with radiologic findings and preceding medical treatment. AJR Am J Roentgenol 2013;201:659–6610.2214/AJR.12.10008CrossRefGoogle ScholarPubMed
Brazeau, P, Vale, W, Burgus, R, Ling, N, Butcher, M, Rivier, J et al. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973;179:77–910.1126/science.179.4068.77CrossRefGoogle ScholarPubMed
Magoo, S, Bhate, K, Kakodkar, P, Gajul, M, Mastud, S. Effect of octreotide in stopping post-surgical chyle leak in neck dissection: a systematic review. J Oral Biol Craniofac Res 2022;12:737–4110.1016/j.jobcr.2022.08.018CrossRefGoogle ScholarPubMed
National Institute for Health and Care Excellence. Octreotide. In: British National Formulary. London: NICE, 2025Google Scholar
Markham, KM, Glover, JL, Welsh, RJ, Lucas, RJ, Bendick, PJ. Octreotide in the treatment of thoracic duct injuries. Am Surg 2000;66:116510.1177/000313480006601215CrossRefGoogle ScholarPubMed
Figure 0

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist flow diagram showing the strategy for systematic review.Figure 1 long description.

Figure 1

Table 1. Baseline characteristics of publications included in the analysis (n/a-not available)Table 1 long description.

Figure 2

Table 2. Primary outcomes (length of time for resolution of chyle leak in patients who had octreotide) and secondary outcomes of the study (length of in-patient stay, percentage of patients who had surgical management). (MCT = Medium Chain Triglycerides, TPN = Total Parental Nutrition, n/a = Not available.)Table 2 long description.