“Therapeutic Use of Octreotide in the Management of Post-Cardiac Surgery

Chylothorax in Children: 12-year Single Center Experience”

Tauhid Ahmed Bhuiyan, PharmDStaff/Clinical Pharmacist, NICU

Pharmaceutical Care Division, KFSH&RC

Background• What is “chylothorax”?

• Rare complication characterized by accumulation of “milky” chylous fluid into the pleural space• chylomicrons, triglycerides, WBCs, T-lymphocytes, fat-soluble vitamins, or extravasated plasma

proteins

• Reported incidence in children varies between 0.25% to 9.2%

• Etiology in post-cardiac surgery settings:• Stretch tear of the thoracic duct mainly from trauma of complex congenital heart surgeries

• e.g. Norwood, Bi-directional Glenn, or Fontan procedure

• Complications: • Malnutrition, poor wound healing, infections, fluid and electrolyte imbalances, prolonged

mechanical ventilation and device utilizations, frequent admissions in the intensive care unit (ICU), and/or death

• No standardized protocol or clinical practice guidelines till today

• Individual institutions have their management strategies developed based on existing literature

• In KFSH&RC: “Stepwise approach” starts with supportive measures followed by:1. Medium-chain triglycerides (MCT) or Fat Free Formula

2. Parenteral Nutrition (PN) or Nothing Per Oral (NPO) 3. Corticosteroids (e.g. Prednisone 1 mg/kg/day)

4. Octreotide: 0.5-4 µg/kg/hr as continuous infusion5. Surgical repair or chemical intervention

Management of Chylothorax

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Octreotide• Somatostatin analog, functions as decreasing the blood flow to hepatic, portal, and

splanchnic circulations less chylous flow through thoracic duct

• First introduced for treatment of chylothorax in 1998 by Rimensberger et al.

• Gained favorable clinical implications over others due to its longer half-life, higher potency, and better side-effects profile

• Reported side effects:• Transient hyper/hypo-glycemia; transient hypothyroid function; mild abdominal

distension, vomiting, diarrhea; elevation of hepatic transaminases; and rarely necrotizing enterocolitis

Literature on Octreotide Use• Mainly published as case reports and case series

• A systemic review of all reported cases (2003-2005)• N = 35• Average octreotide dose: 68 µg/kg/hr • Resolution of chylothorax was achieved at a median duration of 5-7 days• No major adverse effects were seen • Limitations: lacks construct validity since the study incorporated all types of chylothoraces

• A retrospective chart review (10-year) by Caverly L. et al• N = 19 • Resolution achieved 63% (n=12) of cases at a median duration of 8 days [range: 4-21]• No major adverse effects were seen• Limitations: smaller sample size; did not define their resolution criteria

Study Design• Retrospective cohort study: January 2003 – August 2015

• Main objective: • Assess the efficacy and safety of octreotide as a therapeutic option in post-cardiac surgery

chylothorax

• Inclusion criteria:• Patient <18 years of age who received octreotide for management of post-cardiac surgery

chylothorax

• Exclusions:• Pleural effusion unrelated to cardiac surgery• Non-confirmatory diagnosis of chylothorax• Inadequate or missing data• Octreotide used for indications other than post-cardiac surgery induced chylothorax

Endpoints• Primary efficacy endpoint: “Resolution of chylothorax”

• Other endpoints: • Mean dose and duration of octreotide therapy• Time (days) from cardiac surgery to chylothorax diagnosis• Time (days) to start nutritional intervention after chylothorax diagnosis• Time (days) to octreotide therapy following chylothorax diagnosis

• Major safety endpoint:• Any adverse drug reactions leading to octreotide therapy discontinuation

1. Complete resolution: total chylous drainage <2 mL/kg/day

2. Partial resolution: radiologic or biochemical features suggestive of significant improvement (per treating physician)3. Resolution failure: patients failed to improve chylothoraces following octreotide therapy

Statistical Analysis

• Percent (%) to summarize dichotomous variables

• Student’s t-test: compare means between each group

• Pearson Correlation Coefficient: correlations between two independent variables

• SPSS version 20.0 software for statistical analyses

Results

Study Profile

Total excluded: 17

Exclusion reasons:

Octreotide used for other indications: 8

Missing or insufficient data: 5

Pleural effusion unrelated to chylothorax: 3

Non-confirmatory diagnosis of chylothorax: 1

Initially identified patients:

46 patients

29 patients included for analysis

Base

line

Dem

ogra

phic

s

Efficacy Endpoints

• Total resolution:• 18 (62%) patients

• Resolution failure:• 11 (38%)

28%38%

34%

Complete

Partial

Failure

Efficacy Endpoints Cont.

Correlation: Chylous Output to Octreotide Initiation

Safety Endpoints

• Transient hyperglycemia, n (%): • 13 (45%) [blood glucose level: 10.4 to 24.9 mmol/L ]

• Minor gastrointestinal symptoms (abdominal distension), n(%):• 1 (3%)

• Tachycardia (heart rate >150 bpm), n(%):• 3 (10%)

Study Limitations

• Our limited experience with octreotide hindered us to start with higher doses

• Patient stratification (high risk vs. low risk)

Impact on Clinical Practice • By far the best available evidence in this clinical settings

• Largest (sample size) and longest retrospective cohort study

• First in Saudi Arabia

• Enabled us to identify the appropriate dose, duration, and the timing to initiation of octreotide therapy

• Provided us future guidance on proper management

Authors’ Conclusion

“Therapeutic use of octreotide along with standard treatment modalities for the management of post-cardiac surgery chylothorax holds a promising benefit with acceptable safety profile”

Acknowledgements

1. Abdulrazaq S. Aljazairi, Head, Medical/Critical Care Pharmacy Services

2. Rayd A. Almehizia, Cardiovascular Clinical Pharmacy Specialist

3. Abdullah H. Alwadai, Consultant, Pediatric Cardiac Intensivist

4. Abdelmoneim M. Eldali, Department of Biostatistics

Thank you