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 space1,2,3,4,5. 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 fetal trachea5,6,7,8,9,10,11,12,13. The use of these catheters and external sensors (distal to the measurement site) may dampen the pressure signal and necessitate restricted movement of the ewe for continuous measurement or measurements obtained at intervals across gestation. This study aimed to develop a method that allows continuous monitoring of fetal intratracheal and amniotic pressure in unrestrained pregnant animals. The continuous measurements of fetal intratracheal and amniotic pressure will provide a complete understanding of how these pressures change throughout the day over the course of gestation.
Human fetuses with congenital diaphragmatic hernia (CDH) have lung hypoplasia due to herniation of the stomach, the bowel, and the liver (in the most severe cases) into the chest cavity. Lung hyperplasia in infants with tracheal atresia (narrowing of the trachea) highlighted the potential of therapeutic tracheal occlusion for antenatal treatment of CDH14. Tracheal occlusion using an intra-tracheal balloon reduces the severity of lung hypoplasia in fetuses with CDH but at the cost of an increased risk of premature birth15,16,17. An additional risk of aspiration or suffocation exists if the balloon is not removed before birth. Consequently, current tracheal occlusion protocols require a second fetal procedure to remove the balloon occlusion before birth17. The optimal occlusion pressure and duration required to improve lung hypoplasia with tracheal occlusion is unknown, but this knowledge is vital for the optimization of in utero corrective treatments for CDH.
We tested the method using fetal lambs with a surgically created diaphragmatic hernia with and without an occluded trachea.
Protocol
Representative Results
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 hypoplasia20,21,22,23. Tracheal occlus…
Disclosures
The authors have nothing to disclose.
Acknowledgements
The authors acknowledge the surgical assistance of Jane Choi (University of Western Australia), Ellen Williams (University of Western Australia), and Veena Kurup (University of Western Australia), as well as the husbandry care of the Animal Care Services staff at the University of Western Australia. This study was supported by the Telethon Perth Children's Research Fund, National Health and Medical Research Council RF 1077691 (JJP), Metropolitan Health and Medical Research Infrastructure Fund (West Australian Government), and Australian International Research Training Program (MD).
Materials
| 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 |
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