Intercostal Nerve Cryoablation Versus Epidural Analgesia for Nuss Repair of Pectus Excavatum

Pectus Excavatum Clinical Trial

— ICE  

Official title:

Intercostal Nerve Cryoablation Versus Thoracic Epidural Analgesia for Minimal Invasive Nuss Repair of Pectus Excavatum: a Randomized Clinical Trial (ICE Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05731973
• Other study ID #: Z2023005
• Status: Recruiting
• Phase: N/A
• Start date: December 8, 2023
• Est. completion date: September 2025

Study information

• Verified date: January 2024
• Source: Zuyderland Medisch Centrum
• Contact: Erik R De Loos
• Phone: 088-4597777
• Email: e.deloos[@]zuyderland.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective of the current study is to determine the impact of intercostal nerve cryoablation on postoperative length of hospital stay compared to standard pain management of young pectus excavatum patients (12-24 years) treated with the minimal invasive Nuss procedure. The study is designed as a single center, prospective, unblinded, randomized clinical trial.

Description:

Rationale: The minimal invasive Nuss procedure is currently considered the treatment of choice for pectus excavatum. This procedure is usually associated with severe postoperative pain as great forces are employed on the thoracic cage to correct the sternal depression. Pain is the main limiting factor for early discharge. Epidural analgesia is currently considered gold standard for postoperative pain treatment. Alternative pain management strategies (e.g., patient-controlled analgesia and paravertebral nerve block) have also been described but fail in accomplishing adequate prolonged post-operative pain management. Alternatively, continuous use of opioids comes with side-effects like severe nausea, urinary retention and obstipation. Intercostal nerve cryoablation seems a promising novel technique for postoperative analgesia. Prior studies comparing intercostal cryoablation to other pain treatment modalities after pectus excavatum repair through the minimal invasive Nuss procedure report promising results, but pose significant limitations (e.g., small sample size, retrospective nature with non-matched patient groups or considerable confounders).

Objective: Primary objective of the current study is to determine the impact of intercostal nerve cryoablation on postoperative length of hospital stay compared to standard pain management of young pectus excavatum patients treated with the minimal invasive Nuss procedure.

Study design: The study protocol is designed for a single center, prospective, unblinded, randomized clinical trial.

Study population & intervention: Intercostal nerve cryoablation will be compared to thoracic epidural analgesia in young pectus excavatum patients (i.e., 12-24 years of age) treated with the minimal invasive Nuss procedure. Block randomization, including stratification based on age (12-16 years and 17-24 years) and sex, with an allocation ratio of 1:1 will be performed.

Main study parameters/endpoints: Postoperative length of hospital stay will be recorded as the primary endpoint. Secondary outcomes include: 1) pain intensity; 2) operative time; 3) opioid usage; 4) complications, including neuropathic pain; 5) creatine kinase activity; 6)intensive care unit admissions; 7) readmissions; 8) postoperative mobility; 9) health related quality of Life; 10) days to return to work/school; 11) number of postoperative outpatient visits and 12) hospital costs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks for study participants are negligible as the cryoablation technique has already been effectively used in the Nuss procedure without any serious side effects. Also, participants will be monitored daily by nursing staff and surgeons while admitted to the hospital. Burden associated with participation in the current study consists of completion of several questionnaires preoperatively and postoperatively.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 24 Years

Eligibility

Inclusion Criteria:

• Patients undergoing the minimal invasive Nuss procedure for surgical repair of pectus excavatum.

• Young patients (12-24 years of age) according to the definition used by the World Health Organization. This cut-off point is chosen to create a more homogenous patient sample, as the thoracic cage is fully matured by the age of 24, in size and density, which will have an effect on postoperative pain.

Exclusion Criteria:

• A chest wall deformity other than pectus excavatum;

• Opioid use in the 3 months prior to surgery;

• Pain syndrome (e.g., fibromyalgia) or neuropathic pain prior to surgical repair of pectus excavatum;

• Connective tissue disease (e.g., Marfan syndrome, Ehlers-Danlos syndrome);

• Previous thoracic surgery or pectus excavatum repair;

• Contraindication for intercostal nerve cryoablation or thoracic epidural analgesia (e.g., patient refusal, infection at the site of cannulation, uncontrolled systemic infection, bleeding diathesis, increased intracranial pressure, mechanical spine obstruction);

• Psychiatric disease currently receiving treatment;

• Not mastering the Dutch language;

• Participation in another clinical trial that may interfere with the current trial.

Related Conditions & MeSH terms

• Funnel Chest
• Pectus Excavatum

Intervention

Procedure:
• Intercostal nerve cryoablation
Intercostal nerve cryoablation is applied during Nuss procedure.

Drug:
• Thoracic epidural analgesia (continuous infusion with sufentanyl (1 µg/ml) and bupivacaine (1.25 mg/ml))
Thoracic epidural is placed prior to Nuss procedure
• Intercostal nerve block (single shot bupivacaine (1.25 mg/ml))
Single shot bupivacaine (1.25 mg/ml) intercostal nerve blocks are placed just anterior to the side of the cryoablation.
• Opioids (oxycodone with prolonged discharge 10 mg PO every 12 hours and oxycodone 5 mg every 6 hours, as needed)
Opioids

Locations

Country	Name	City	State
Netherlands	Zuyderland Medical Center	Heerlen	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Zuyderland Medisch Centrum	AtriCure, Inc.

Country where clinical trial is conducted

Netherlands, 

References & Publications (16)

Abdel Shaheed C, McLachlan AJ, Maher CG. Rethinking "long term" opioid therapy. BMJ. 2019 Nov 29;367:l6691. doi: 10.1136/bmj.l6691. No abstract available. — View Citation

Aiken TJ, Stahl CC, Lemaster D, Casias TW, Walker BJ, Nichol PF, Leys CM, Abbott DE, Brinkman AS. Intercostal nerve cryoablation is associated with lower hospital cost during minimally invasive Nuss procedure for pectus excavatum. J Pediatr Surg. 2021 Oct — View Citation

Cadaval Gallardo C, Martinez J, Bellia-Munzon G, Nazar M, Sanjurjo D, Toselli L, Martinez-Ferro M. Thoracoscopic cryoanalgesia: A new strategy for postoperative pain control in minimally invasive pectus excavatum repair. Cir Pediatr. 2020 Jan 20;33(1):11- — View Citation

Croitoru DP, Kelly RE Jr, Goretsky MJ, Lawson ML, Swoveland B, Nuss D. Experience and modification update for the minimally invasive Nuss technique for pectus excavatum repair in 303 patients. J Pediatr Surg. 2002 Mar;37(3):437-45. doi: 10.1053/jpsu.2002. — View Citation

Daemen JHT, de Loos ER, Vissers YLJ, Bakens MJAM, Maessen JG, Hulsewe KWE. Intercostal nerve cryoablation versus thoracic epidural for postoperative analgesia following pectus excavatum repair: a systematic review and meta-analysis. Interact Cardiovasc Th — View Citation

Dekonenko C, Dorman RM, Duran Y, Juang D, Aguayo P, Fraser JD, Oyetunji TA, Snyder CL, Holcomb GW 3rd, Millspaugh DL, St Peter SD. Postoperative pain control modalities for pectus excavatum repair: A prospective observational study of cryoablation compare — View Citation

Graves CE, Moyer J, Zobel MJ, Mora R, Smith D, O'Day M, Padilla BE. Intraoperative intercostal nerve cryoablation During the Nuss procedure reduces length of stay and opioid requirement: A randomized clinical trial. J Pediatr Surg. 2019 Nov;54(11):2250-22 — View Citation

Harbaugh CM, Johnson KN, Kein CE, Jarboe MD, Hirschl RB, Geiger JD, Gadepalli SK. Comparing outcomes with thoracic epidural and intercostal nerve cryoablation after Nuss procedure. J Surg Res. 2018 Nov;231:217-223. doi: 10.1016/j.jss.2018.05.048. Epub 201 — View Citation

Morikawa N, Laferriere N, Koo S, Johnson S, Woo R, Puapong D. Cryoanalgesia in Patients Undergoing Nuss Repair of Pectus Excavatum: Technique Modification and Early Results. J Laparoendosc Adv Surg Tech A. 2018 Sep;28(9):1148-1151. doi: 10.1089/lap.2017.0 — View Citation

Nuss D, Kelly RE Jr. Indications and technique of Nuss procedure for pectus excavatum. Thorac Surg Clin. 2010 Nov;20(4):583-97. doi: 10.1016/j.thorsurg.2010.07.002. — View Citation

Nuss D. Minimally invasive surgical repair of pectus excavatum. Semin Pediatr Surg. 2008 Aug;17(3):209-17. doi: 10.1053/j.sempedsurg.2008.03.003. — View Citation

Qi J, Du B, Gurnaney H, Lu P, Zuo Y. A prospective randomized observer-blinded study to assess postoperative analgesia provided by an ultrasound-guided bilateral thoracic paravertebral block for children undergoing the Nuss procedure. Reg Anesth Pain Med. — View Citation

Sertcakacilar G, Kose S. Bilateral PECS II Block is Associated with Decreased Opioid Consumption and Reduced Pain Scores for up to 24 hours After Minimally Invasive Repair of Pectus Excavatum (Nuss Procedure): A Retrospective Analysis. J Cardiothorac Vasc — View Citation

Sujka J, Benedict LA, Fraser JD, Aguayo P, Millspaugh DL, St Peter SD. Outcomes Using Cryoablation for Postoperative Pain Control in Children Following Minimally Invasive Pectus Excavatum Repair. J Laparoendosc Adv Surg Tech A. 2018 Nov;28(11):1383-1386. — View Citation

Sun RC, Mehl SC, Anbarasu CR, Portuondo JI, Espinoza AF, Whitlock R, Mazziotti MV. Intercostal cryoablation during Nuss procedure: A large volume single surgeon's experience and outcomes. J Pediatr Surg. 2021 Dec;56(12):2229-2234. doi: 10.1016/j.jpedsurg. — View Citation

Zobel MJ, Ewbank C, Mora R, Idowu O, Kim S, Padilla BE. The incidence of neuropathic pain after intercostal cryoablation during the Nuss procedure. Pediatr Surg Int. 2020 Mar;36(3):317-324. doi: 10.1007/s00383-019-04602-1. Epub 2019 Nov 23. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of hospital stay	Number of days of hospital admittance after the Nuss procedure.	Hospitalization period, average of 5 days
Secondary	Pain intensity	Pain intensity at rest and during mobilization. Pain scores will be rated on the numeric rating scale (NRS, 1-10)	Preoperative care unit before surgery, in the morning on postoperative day 1 and 2, and 7 days, 14 days, 3 months and 6 months post operation
Secondary	Operative time	Operative time in minutes. Duration of cryoablation will be assessed separately. Operative time will not include the time needed for the placement of the thoracic epidural as placement will be performed in the preoperative care unit.	During Nuss procedure
Secondary	Opioid usage	A) Intraoperative administered opioids; B) Opioid usage during postoperative day 0, 1 and 2 at the recovery unit and surgical ward; C) Opioid usage within the first 2 weeks after surgery. Opioid usage will be converted to oral morphine milligram equivalents (MME).	postoperative day 1 and 2, and first 2 weeks after surgery
Secondary	Complications	Complications graded according to the Clavien-Dindo classification. The most common procedure- and analgesia-related complications are defined in Supplementary Materials Table 1-2 for transparency, including neuropathic pain. Occurrence of neuropathic pain will be actively monitored during the hospitalization period, and during all follow-up appointments.	6 months postoperative
Secondary	Creatine kinase (CK) activity	CK levels will be assessed prior to the surgical procedure (i.e., baseline measurement during routine blood evaluation on the day of surgery) and on postoperative day 1. CK levels will be denoted in U/L.	Preoperative and day 1 postoperative
Secondary	Intensive care unit admission	Intensive care unit admission due to the occurrence of perioperative complications in absolute numbers	Hospitalization period, average of 5 days
Secondary	Length of intensive care unit admission	Length of admission due to the occurrence of perioperative complications in absolute numbers.	Hospitalization period, average of 5 days
Secondary	Number of readmissions	Number of readmissions denoted as absolute numbers.	6 months postoperative
Secondary	Length of readmissions	length of readmissions denoted as absolute numbers.	6 months postoperative
Secondary	Degree of mobility	Degree of mobility measured on a 4-point scale (i.e., 1. on the bed, 2. to the chair, 3. to the toilet, 4. outside the patient's hospital room) during postoperative day 1 and 2.	Postoperative day 1 and 2
Secondary	HRQOL - PEEQ	HRQOL, measured by the Dutch version of the pectus evaluation questionnaire (PEEQ). The PEEQ is a validated disease specific questionnaire evaluating the quality of life in pectus excavatum patients (37,38).	Before surgery as a baseline measurement, and at 2 weeks, 3 months and 6 months after the surgical procedure
Secondary	HRQOL - SF-36	HRQOL, measured by the Dutch version of the short form health survey (SF-36)(37-40). The SF-36 is a generic questionnaire that taps health in eight dimensions (39).	Before surgery as a baseline measurement, and at 2 weeks, 3 months and 6 months after the surgical procedure
Secondary	HRQOL - EQ-5D-5L	HRQOL, measured by the Dutch version of the EuroQol 5 dimensions 5 levels (EQ-5D-5L) (37-40). For the EQ-5D-5L, participants will rate their health in 5 dimensions on 5 levels and will give an overall score of their health on a visual analogue scale (VAS) (40).	Before surgery as a baseline measurement, and at 2 weeks, 3 months and 6 months after the surgical procedure
Secondary	Days to return to work/school	Days to return to work/school, reported as days between discharge from hospital and return to work or school.	6 months postoperative
Secondary	Postoperative visits	Number of postoperative outpatient visits and telephone appointments denoted as absolute numbers in the first 6 months after the surgical procedure.	6 months postoperative
Secondary	Hospital costs	Hospital costs, reported as hospital costs during initial hospitalization (e.g., medication, patient care supply, surgical equipment), and hospital costs after discharge until 6 months follow-up (e.g., medications, outpatient visits, (opioid related) readmissions).	6 months postoperative

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