Continuous Telemetric In Utero Tracheal Pressure Measurements in Fetal Lambs

Summary

Optimization of occlusion pressure and duration required to improve lung hypoplasia with tracheal occlusion is essential to improve in utero corrective treatments for congenital diaphragmatic hernia (CDH). This study reports a new method for continuous measurement of the tracheal pressure in an occluded and unoccluded fetal lamb surgical model of CDH.

Abstract

Normal in utero lung development and growth rely upon the expansion of airspaces and the controlled efflux of lung liquid into the amniotic space. Infants with congenital diaphragmatic hernia (CDH) also have lung hypoplasia due to occupation of the chest cavity by the stomach and bowel and, in the most severe cases, the liver. Balloon tracheal occlusion reduces the severity of lung hypoplasia in fetuses with CDH but increases the risk of premature birth. Understanding the optimal occlusion pressure and duration required to improve lung hypoplasia with tracheal occlusion is essential to improving in utero corrective treatments for CDH. The study reports a new method for continuous measurement of the intratracheal and amniotic pressures in an unoccluded and occluded fetal lamb surgical model of CDH. Time-pregnant Merino ewes underwent two recovery hysterotomies: the first at ~80 days of gestation to create the CDH, and the second at ~101 days of gestation to occlude the fetal trachea and implant an intratracheal and amniotic pressure measurement device. Lambs were delivered at ~142 days, and the pressure measurement device was removed and cleaned. The data were downloaded and filtered using a 6 h window. Transrespiratory pressure was calculated.

Introduction

Normal lung development and growth rely upon the expansion of the potential airspaces with fetal lung liquid and the controlled efflux of the lung liquid into the amniotic space^1,2,3,4,5. Fetal lung liquid production and the resistance of the upper airways create an in utero intrathoracic pressure¹. Historically, in utero measurements of fetal airway pressures were obtained using external pressure sensors via catheters tunneled through the abdominal wall to the feta....

Protocol

The protocol adhered to the Australian National Health and Medical Research Council Australian code for the care and use of animals for scientific purposes¹⁸. The University of Western Australia Animal Ethics Committee prospectively approved the protocol (RA3/100/1596). Sheep were sourced from the University of Western Australia (UWA) Ridgefield farm (2018-2020). The sheep were introduced to the AAALAC-accredited UWA Large Animal Facility 2-3 weeks prior to surgical intervention. Sheep were initia.......

Discussion

Fetal lung liquid fills the potential airspaces during gestation and is vital for normal lung development¹. Altering the normal lung liquid amount and pressure affects fetal lung growth: narrowing or constriction of the fetal trachea leads to lung hyperplasia; conversely, oligohydramnios and chronic drainage of lung fluid cause lung hypoplasia^20,21,22,23. Tracheal occlus.......

Materials

Name	Company	Catalog Number	Comments
1.59 mm (outside diameter, OD) to 3.18 mm (OD) connector	Qosina	11913
3.18 mm (OD) to 3.18 mm (OD) connector	Qosina	11684
70 % Alcohol	Henry Schein	1127067
Absorbable poliglecaprone 25 monofilament 3-0	Riverpoint Medical	Q316
Absorbable polydioxanone monofilament 1	Riverpoint Medical	D879
Absorbable polyglactin 910 braided 2-0	Riverpoint Medical	V317
Absorbable polydioxanone monofilament 5-0	Riverpoint Medical	D303
Acepromazine	Ceva Animal Health	APVMA No: 36680
Babcock, uterine forceps 6.25 inch	Roboz	RS-8022
Betamethasone	Merck Sharp & Dohme	Aust R 18777
Blade, size 10	Becton Dickinson	371110
Blade, size 15	Becton Dickinson	371115
Bupivacaine	Pfizer Australia Pty Ltd	AUST R 11312
Cefazolin	AFT pharmaceuticals	AUST R 171582
Chlorhexidine	Henry Schein	0404-0175-02
Endotracheal tube (size 8.0)	Jorgen Kruuse	272411
Forceps, Potts-Smith	Roboz	RS-5314
Iodine solution (10 %)	Henry Schein	6907281
Isoflurane	Piramal Critical Care	APVMA No: 53120/112272 M. L. No.:220/AP/MD/96/B&F/R
Ketamine	Ceva Animal Health	APVMA 37711/58317 KETALAB04
Hartmanns Solution	Baxter	AUST R 48510
Hemostats, Mosquito forceps curved delicate	Roboz	RS-7271
Medroxyprogesterone acetate	Pfizer Australia Pty Ltd	AUST R 12300
Meloxicam	Ilium	APVMA Approval No.: 62535/127884 LI0119V1
Methocel	Colorcon	ID34435
Microcuff endotracheal tube (3.0)	Halyard	35111
Midazolam	Mylan	AUST R 160205
Morphine	Pfizer Australia Pty Ltd	AUST R 101240
Needle, 22 G	Becton Dickinson	305155
Needle, 27 G	Becton Dickinson	305109
Nonabsorbable nylon monofilament 4-0	Riverpoint Medical	662BL
Nonabsorbable polypropylene monofilament 2-0	Riverpoint Medical	P8411
OpSite Transparent Film	Smith and Nephew	66000040
Oxytetracycline	Norbrook	APVMA Approval No: 53087/49616
Peracetic acid/hydrogen peroxide	Medivators Inc	ref: 78401-649
Piperacillin/Tazobactam	Sandoz Pty Ltd	AUST R 140840
Scissors, Metzenbaum Surgical 7 inch straight	Roboz	RS-6955SC
Scissors, Vannas 0.15 mm tip width	Roboz	RS-5618
Silicone tubing (1.59 mm inside diameter)	Qosina	T2013
Suction catheter (5 French)	Covidien	30500
Syringe, 1 mL	Becton Dickinson	309659
Syringe, 10 mL	Becton Dickinson	309604
Syringe, 60 mL	Becton Dickinson	309654
Thiopentone sodium	Jurox Pty Ltd	APVMA No. 51520/5g/0809
Transdermal fentanyl patch	Janssen-Cilag Pty Ltd	AUST R 112371