Use of Indocyanine Green During Primary Repair of Oesophageal Atresia and Distal Tracheo-oesophageal Fistula

Study Overview
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Brief Summary
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This study aims to look at babies having a primary or delayed primary oesophageal repair for OA with dTOF to evaluate if using Indocyanine green (ICG) and near infrared fluorescence (NIRF) can decrease the rates of anastomotic leaks and/or predict which patients they will happen in. The latter evaluation would help counsel parents and mean that further research can evaluate if other tactics can prevent the leak being a moderate or severe problem. These may include, but not be limited to, extra anastomotic sutures, insertion of a chest drain at the time of surgery (if this had not previously been considered) delaying oral feeding or using medications to dry up the saliva prophylactically (these medications have been shown to reduce the length of time it takes leaks to seal). Any technique that can reduce leak rates in oesophageal atresia is to be welcomed. Additionally ICG may artifactually affect both peripheral oxygen readings (cause a transient decrease) and cerebral near infrared spectroscopy (NIRS) values (cause a transient increase). This is due to the temporary, dose dependent, interference of the dye with the mechanism of action of the monitoring rather than a physiological effect on oxygen levels. To date there has been no study investigating the effects of ICG on oxygen saturation and cerebral NIRS in neonates undergoing OA and/or dTOF repair. The theory is an extension from adult practice following oesophagectomy for cancer where there was a reduction in anastomotic leaks when using ICG/NIRF perfusion assessment. Another study in bariatric surgery using an enteral ICG/NIRF assessment was highly sensitive for anastomotic leaks allowing management of them intra-operatively. Objectives are to Identify if the appearances of ICG/NIRF can predict anastomotic leaks Identify if the ICG/NIRF images would engender a change in operative management leading to a reduced leak rate Give a detailed report on the effects of ICG on oxygen readings This would be a cohort pilot study of 20 patients with the aim of informing a subsequent multi-centre Randomised controlled trial

Detailed Description
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Anastomotic leaks can have wide ranging consequences. If they can be predicted and/or prevented clinical outcomes for patients would be improved along with shorter length of stay and reduced cost to the national health service (NHS) in the short, medium, and long term. These patients would require less bed days both on inpatient wards and paediatric intensive care units enabling the management of other children. This study will evaluate if ICG/NIRF tissue perfusion diagnostics can show if the fistula (distal oesophagus) end is ischaemic (has poor blood flow) prior to anastomosis. Ischaemic ends are well recognised to relate to leakage although in OA the role of mucosal apposition is poorly understood. This intervention would afford the operator the opportunity to perform a fully vascularised join if feasible and also indicate if ischaemia predicts anastomotic leaks. It will also evaluate if post-anastomosis intravenous and enteral dosing of ICG with NIRF assessment is able to predict those who will suffer from a leak whether that be clinical or radiological. There is little data on the effect of ICG on peripheral oxygen saturation readings, or of its effect on near infrared spectroscopy readings in neonates. This study will record the effects on peripheral saturation and near-infrared spectroscopy readings which are used routinely in babies having this type of surgery. It will compare these readings to arterial blood oxygenation readings from a blood gas analyser. Blood gases are routinely taken during this procedure and so this will not involve any extra blood testing over and above what is ordinarily performed.

Official Title
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Indocyanine Green (ICG) and Near Infrared Fluorescence (NIRF) Guided Assessment of the Bowel and Oesophageal Anastomosis During Repair of Oesophageal Atresia With Distal Trachea-oesophageal Fistula (OA/dTOF): a Cohort Pilot Study

Conditions
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Tracheo-Esophageal Fistula With Atresia of Esophagus

Intervention / Treatment
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* Drug: Indocyanine green


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-operative Diagnosis of oesophageal atresia with distal trachea-oesophageal fistula (OA/dTOF) Plan for primary or delayed primary oesophageal anastomosis Intra-operative Diagnosis of OA/dTOF confirmed by standard methods Primary or delayed primary oesophageal anastomosis considered clinically, physiologically, and technically feasible Exclusion Criteria: Pre-operative Under 2.5kg in weight Complex cardiac disease Allergic to ICG Allergic to iodine or iodides Hyperthyroidism Chronic Kidney Disease stage V Unwilling to participate Those in whom exchange transfusion is indicated due to hyperbilirubinemia Intra-operative • Anaesthetic concerns contra-indicating the use of intravenous ICG due its temporary effect on oxygen saturation readings prior to injection of ICG

Ages Eligible for Study
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Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Consecutive patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICG<br>Patients in this single arm will receive ICG during their surgery | Drug: Indocyanine green<br>* Intravenous and endoluminal dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intravenous ICG | Number of patients with abnormal perfusion will have a clinical and/or radiological anastomotic leak | Within two weeks of surgery | 
| Enteral ICG | Number of patients in whom ICG given enterally shows an anastomotic leak | Within two weeks of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delphi | Number of patients in whom ICG given prior to anastomosis causes a change in intra-operative plan | Within a year following surgery | 
| Peripheral oxygen saturations (SpO2) | In how many patients does the intravenous injection of ICG alter the peripheral oxygenation and/or near infrared spectroscopy readings. | Within a year following surgery |