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

Official title

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

Overview

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 1. Identify if the appearances of ICG/NIRF can predict anastomotic leaks 2. Identify if the ICG/NIRF images would engender a change in operative management leading to a reduced leak rate 3. 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

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.

Interventions

• Drug Indocyanine green
  Intravenous and endoluminal dosing

Primary outcome measures

• Intravenous ICG [Time frame: Within two weeks of surgery]
• Enteral ICG [Time frame: Within two weeks of surgery]

Secondary outcome measures (2)

• Delphi [Time frame: Within a year following surgery]
• Peripheral oxygen saturations (SpO2) [Time frame: Within a year following surgery]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United Kingdom · 1 center

• Birmingham children's hospital — Birmingham

Publications

• Kalmar CL, Reed CM, Peery CL, Salzberg AD. Intraluminal indocyanine green for intraoperative staple line leak testing in bariatric surgery. Surg Endosc. 2020 Sep;34(9):4194-4199. doi: 10.1007/s00464-020-07606-4. Epub 2020 May 8. PMID 32385707
• Schmedding A, Wittekindt B, Schloesser R, Hutter M, Rolle U. Outcome of esophageal atresia in Germany. Dis Esophagus. 2021 Apr 7;34(4):doaa093. doi: 10.1093/dote/doaa093. PMID 32995846
• Long AM, Tyraskis A, Allin B, Burge DM, Knight M. Oesophageal atresia with no distal tracheoesophageal fistula: Management and outcomes from a population-based cohort. J Pediatr Surg. 2017 Feb;52(2):226-230. doi: 10.1016/j.jpedsurg.2016.11.008. Epub 2016 Nov 13. PMID 27894760
• Burge DM, Shah K, Spark P, Shenker N, Pierce M, Kurinczuk JJ, Draper ES, Johnson PR, Knight M; British Association of Paediatric Surgeons Congenital Anomalies Surveillance System (BAPS-CASS). Contemporary management and outcomes for infants born with oesophageal atresia. Br J Surg. 2013 Mar;100(4):515-21. doi: 10.1002/bjs.9019. Epub 2013 Jan 18. PMID 23334932
• Allin B, Knight M, Johnson P, Burge D; BAPS-CASS. Outcomes at one-year post anastomosis from a national cohort of infants with oesophageal atresia. PLoS One. 2014 Aug 25;9(8):e106149. doi: 10.1371/journal.pone.0106149. eCollection 2014. PMID 25153838
• Comella A, Tan Tanny SP, Hutson JM, Omari TI, Teague WJ, Nataraja RM, King SK. Esophageal morbidity in patients following repair of esophageal atresia: A systematic review. J Pediatr Surg. 2021 Sep;56(9):1555-1563. doi: 10.1016/j.jpedsurg.2020.09.010. Epub 2020 Sep 19. PMID 33051081
• Weber F, Scoones GP. A practical approach to cerebral near-infrared spectroscopy (NIRS) directed hemodynamic management in noncardiac pediatric anesthesia. Paediatr Anaesth. 2019 Oct;29(10):993-1001. doi: 10.1111/pan.13726. Epub 2019 Aug 29. PMID 31437328
• Bishay M, Giacomello L, Retrosi G, Thyoka M, Nah SA, McHoney M, De Coppi P, Brierley J, Scuplak S, Kiely EM, Curry JI, Drake DP, Cross KM, Eaton S, Pierro A. Decreased cerebral oxygen saturation during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia in infants. J Pediatr Surg. 2011 Jan;46(1):47-51. doi: 10.1016/j.jpedsurg.2010.09.062. PMID 21238638

Identifiers

NCT: NCT05735964 · 22/BC/ONC/NO/633

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗