An Animal Model for Endotracheal Tube–Related Laryngeal Injury Using Hypoxic Ventilation

Gordin, Arie; Chadha, Neil K.; Campisi, Paolo; Luginbuehl, Igor; Taylor, Glenn; Forte, Vito

doi:10.1177/0194599810392894

Cited by 16 publications

(38 citation statements)

References 21 publications

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“…Ischemia similarly contributes to poor wound healing. Patients with systemic hypo perfusion are at higher risk for endotracheal tube-related pressure injury to the laryngotracheal mucosa combining to result in cartilage exposure, perichondritis, granulation tissue, and pathologic wound healing leading to scar formation and contracture (1, 14, 16, 24). The risk of local pressure injury on the posterior glottis increases with the length of intubation and size of endotracheal tube (5, 16, 25).…”

Section: Discussionmentioning

confidence: 99%

Predictors of Posterior Glottic Stenosis

Hillel

Karataylı-Özgürsoy

Samad

et al. 2015

Ann Otol Rhinol Laryngol

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Objective To assess intrinsic and extrinsic risk factors in the development of posterior glottic stenosis (PGS) in intubated patients. Methods PGS patients diagnosed between September 2012 – May 2014 at three tertiary care university hospitals were included. Patient demographics, comorbidities, duration of intubation, ETT size, and indication for intubation were recorded. PGS patients were compared to control patients represented by patients intubated in intensive care units (ICU). Results Thirty-six PGS patients were identified. After exclusion, 28 PGS patients (14 male, 14 female) and 112 (65 male, 47 female) controls were studied. Multivariate analysis demonstrated ischemia (p<0.05), diabetes (p<0.01), length of intubation (p<0.01) were significant risk factors for the development of PGS. 14/14 (100%) males were intubated with a size 8 or larger ETT compared to 47/65 (72.3%) male controls (p<0.05). PGS (p<0.01), length of intubation (p<0.001), and obstructive sleep apnea (p<0.05) were significant risk factors for tracheostomy. Conclusion Duration of intubation, ischemia, diabetes mellitus, and large ETT size (8 or greater) in males were significant risk factors for the development of PGS. Reducing the use of size 8 ETTs and earlier planned tracheostomy in high-risk patients may reduce the incidence of PGS and improve ICU safety.

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Section: Discussionmentioning

confidence: 99%

Predictors of Posterior Glottic Stenosis

Hillel

Karataylı-Özgürsoy

Samad

et al. 2015

Ann Otol Rhinol Laryngol

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“…20 In animal models of iLTS, piglets displayed histological signs of injury after 4 hours of intubation, and hypoxic ventilation significantly increased the severity of this injury. 21 …”

Section: Introductionmentioning

confidence: 99%

Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis

Yin

Motz²,

Samad

et al. 2017

Otolaryngol.--head neck surg.

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Objective To elucidate the role of hypoxia and inflammatory pathways in the pathogenesis of iatrogenic laryngotracheal stenosis (iLTS). Study Design 1) Examination of mucosal surface gene expression in human iLTS 2) In vitro comparison of normal and scar laryngotracheal fibroblasts under normoxic and hypoxic conditions Setting Tertiary care hospital in a research university, 2012–2016 Subjects and Methods Brush biopsies were obtained from normal laryngotracheal tissue and scar in iLTS patients; gene expression was compared. Fibroblasts were isolated from normal and scarred trachea and grown in vitro in either a 1% O2 or normoxic environment. Cell growth and gene and protein expression were compared. Statistical analysis utilized a multilevel mixed-effects model. Results Expression of IL-6 (Fold-change = 2.8, p<0.01), myofibroblast marker αSMA (Fold-change = 3.0, p=0.01), and MMP13 (Fold-change = 5.4, p=0.02) was significantly increased in scar biopsy samples compared to normal. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts proliferated significantly faster (n=8, p<0.01 each day). Expression of IL-6 (n=8, Fold-change = 2.6, p<0.01) increased significantly after 12 hours under hypoxia. Expression of αSMA (n=8, Fold-change= 2.0, p=0.03), COL1 (n=8, Fold-change = 1.1), and MMP13 (n=8, Fold-change = 1.6, p=0.01) increased significantly after 48 hours under hypoxia. Scar fibroblasts also proliferated significantly faster under hypoxic conditions, but did not display the same expression profile. Conclusion Human iLTS scar has a myofibroblast phenotype. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts can transdifferentiate into a similar phenotype. These changes may be mediated by IL-6, a fibrosis-related cytokine.

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“…Three control animals were ventilated through a laryngeal mask airway SpO2 = 100%) while undergoing immediate corrosion casting (described below) and three experimental animals were exposed to a 4 hour accelerated intubation injury described elsewhere [7] prior to corrosion casting. The mean age of control piglets was 7.0 +/- 1.0 weeks (range 6–8 weeks) and their mean weight was 14.7 +/- 0.30 kg (range 14.2 - 14.8 kg).…”

Section: Methodsmentioning

confidence: 99%

“…One hypothesis is that when ETT cuff pressure exceeds tissue capillary perfusion pressure, mucosal blood flow is impaired and the resulting edema and ischemic necrosis can lead to formation of fibrotic scar tissue and subglottic stenosis [3,6]. Our group previously developed an animal model of ETT cuff injury that used hypoxia to accelerate the formation of an ischemic subglottic mucosal injury caused by an ETT cuff [7]. We then investigated histopathological changes in the subglottis with varying degrees of ETT cuff pressure and found that constant pressure leads to significant epithelial loss, extensive subepithelial and glandular necrosis, and acute inflammation [7].…”

Section: Introductionmentioning

confidence: 99%

“…Our group previously developed an animal model of ETT cuff injury that used hypoxia to accelerate the formation of an ischemic subglottic mucosal injury caused by an ETT cuff [7]. We then investigated histopathological changes in the subglottis with varying degrees of ETT cuff pressure and found that constant pressure leads to significant epithelial loss, extensive subepithelial and glandular necrosis, and acute inflammation [7]. Though these studies and others have investigated indirect measures of vascular injury, none have directly examined the microscopic vascular features of the subglottic mucosa following ETT-related injury [3,6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Corrosion casting of the subglottis following endotracheal tube intubation injury: A pilot study in Yorkshire piglets

Kus

Sklar

Negandhi

et al. 2013

Journal of Otolaryngology - Head & Neck Surgery

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PurposeSubglottic stenosis can result from endotracheal tube injury. The mechanism by which this occurs, however, is not well understood. The purpose of this study was to examine the role of angiogenesis, hypoxia and ischemia in subglottic mucosal injury following endotracheal intubation.MethodsSix Yorkshire piglets were randomized to either a control group (N=3, ventilated through laryngeal mask airway for corrosion casting) or accelerated subglottic injury group through intubation and induced hypoxia as per a previously described model (N=3). The vasculature of all animals was injected with liquid methyl methacrylate. After polymerization, the surrounding tissue was corroded with potassium hydroxide. The subglottic region was evaluated using scanning electron microscopy looking for angiogenic and hypoxic or degenerative features and groups were compared using Mann–Whitney tests and Friedman’s 2-way ANOVA.ResultsAnimals in the accelerated subglottic injury group had less overall angiogenic features (P=.002) and more overall hypoxic/degenerative features (P=.000) compared with controls. Amongst angiogenic features, there was decreased budding (P=.000) and a trend toward decreased sprouting (P=.037) in the accelerated subglottic injury group with an increase in intussusception (P=.004), possibly representing early attempts at rapid revascularization. Amongst hypoxic/degenerative features, extravasation was the only feature that was significantly higher in the accelerated subglottic injury group (P=.000).ConclusionsSubglottic injury due to intubation and hypoxia may lead to decreased angiogenesis and increased blood vessel damage resulting in extravasation of fluid and a decreased propensity toward wound healing in this animal model.

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An Animal Model for Endotracheal Tube–Related Laryngeal Injury Using Hypoxic Ventilation

Cited by 16 publications

References 21 publications

Predictors of Posterior Glottic Stenosis

Predictors of Posterior Glottic Stenosis

Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis

Corrosion casting of the subglottis following endotracheal tube intubation injury: A pilot study in Yorkshire piglets

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