Endoscopic application of fibrin glue may be a feasible method of treatment for postintubation tracheal lacerations in cats

Molly R. Cohen Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL

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Elizabeth A. Maxwell Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL

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Alexander E. Gallagher Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL

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Diego A. Portela Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL

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 MV, PhD, DACVAA

Abstract

OBJECTIVE

To determine the feasibility of endoscopic application of fibrin glue for the treatment of experimentally induced postintubation tracheal laceration (PITL) in feline cadavers. The secondary objective was to determine the optimal technique for application of the fibrin glue.

ANIMALS

20 feline cadavers (n = 10 fresh and 10 frozen).

PROCEDURES

An experimentally induced tracheal rupture was created via overinflation of an endotracheal tube cuff. After endoscopic identification of the tracheal tear, fibrin glue was instilled into the tracheal defect in either a bridging or filling fashion. Following the procedure, the airway of each cat was examined and leak tested. Length of tear, volume of glue applied, procedural time, and glue efficacy were recorded.

RESULTS

Experimentally induced tracheal lacerations were full thickness with a mean length of 3.27 ± 0.96 cm. A complete seal was attained in 6 of the 9 fresh cadavers when filling the defect with fibrin glue. In the remaining 3 fresh cadavers, air leakage was restricted to the dorsal mediastinum. Bridging the defect with fibrin glue did not attain a seal in fresh or frozen cadavers. The median volume of glue used to fill defects in fresh cadavers was 0.5 mL (range, 0.4 to 2 mL). Procedural time for the application of fibrin glue was 10.5 ± 4.1 minutes for bridging the defect and 7.8 ± 1.5 minutes for filling the defect.

CLINICAL RELEVANCE

Endoscopic application of fibrin glue may be a feasible method of treatment for PITL in cats.

Abstract

OBJECTIVE

To determine the feasibility of endoscopic application of fibrin glue for the treatment of experimentally induced postintubation tracheal laceration (PITL) in feline cadavers. The secondary objective was to determine the optimal technique for application of the fibrin glue.

ANIMALS

20 feline cadavers (n = 10 fresh and 10 frozen).

PROCEDURES

An experimentally induced tracheal rupture was created via overinflation of an endotracheal tube cuff. After endoscopic identification of the tracheal tear, fibrin glue was instilled into the tracheal defect in either a bridging or filling fashion. Following the procedure, the airway of each cat was examined and leak tested. Length of tear, volume of glue applied, procedural time, and glue efficacy were recorded.

RESULTS

Experimentally induced tracheal lacerations were full thickness with a mean length of 3.27 ± 0.96 cm. A complete seal was attained in 6 of the 9 fresh cadavers when filling the defect with fibrin glue. In the remaining 3 fresh cadavers, air leakage was restricted to the dorsal mediastinum. Bridging the defect with fibrin glue did not attain a seal in fresh or frozen cadavers. The median volume of glue used to fill defects in fresh cadavers was 0.5 mL (range, 0.4 to 2 mL). Procedural time for the application of fibrin glue was 10.5 ± 4.1 minutes for bridging the defect and 7.8 ± 1.5 minutes for filling the defect.

CLINICAL RELEVANCE

Endoscopic application of fibrin glue may be a feasible method of treatment for PITL in cats.

Postintubation tracheal laceration (PITL) in cats is an uncommon, but serious injury that can occur secondary to traumatic intubation with a stylet, changing of the cat’s recumbent position without proper disconnection of the endotracheal tube from the anesthetic machine, overinflation of the endotracheal tube cuff, or removal of the endotracheal tube without deflation of the cuff.13 Clinical signs can appear within hours to days and include subcutaneous emphysema (100% [20/20]1, [16/16]2), dyspnea (30% [6/20]1, [5/16]2), and respiratory stridor (15% [3/20]3). Animals with subcutaneous emphysema typically present with pneumomediastinum, which can progress to pneumothorax if pressure is high enough to rupture the mediastinum.1 A prompt diagnosis and treatment are crucial, as clinical complications may result in death.1,2 Although tracheal lacerations can be managed with supportive care, resolution of subcutaneous emphysema is slow and may take 1 to 6 weeks.1,2 Cats with mild to moderate dyspnea and subcutaneous emphysema seem to respond well to oxygen and cage rest, while cats in severe respiratory distress may require emergency surgery.13 Surgery is invasive, may require a median sternotomy, and is often challenging due to the dorsal location of the tear.3 Endoscopic management of tracheal lacerations with the application of fibrin glue has been reported to be successful in humans and is a simple strategy that supplements conservative management of PITL.4,5 The glue covers the tracheal laceration, creating a seal and promoting tissue regeneration.4 There are no published reports on the use of fibrin glue applied endoscopically for tracheal lacerations in animals.

The objectives of this study were (1) to determine the feasibility of the endoscopic application of fibrin glue for the treatment of experimentally induced PITL in feline cadavers, and (2) to determine the optimal technique for application of fibrin glue. It was hypothesized that the endoscopic application of fibrin glue would be easily performed and effective at establishing a seal following experimentally induced tracheal lacerations in feline cadavers when filling the defect.

Materials and Methods

Animals

This project was exempt from Institutional Animal Care and Use Committee approval because no live animals were used, and cats were not euthanized for the purpose of this study. Ten frozen domestic feline cadavers were allowed to thaw at room temperature for 48 hours before the experiment was performed. An additional ten fresh feline cadavers were used within 12 hours of euthanasia. The integrity of the trachea of each cat was initially determined by sustained expansion of the thorax using a manual resuscitation bag generating approximately 22 cm H2O. Cuffed endotracheal tubes were advanced until the cuff was located immediately distal to the vocal cords for testing tracheal integrity. Cats were also examined endoscopically when equipment and expertise were available.

Induction of tracheal injury

The cats were orotracheally intubated with an appropriately sized, cuffed endotracheal tube, with its tip positioned midway between the larynx and the thoracic inlet. The cuff of the endotracheal tube was overinflated in 1-mL increments as previously described.2 Sudden release of pressure or a distinct popping noise was indicative of tracheal rupture. The volume of air required for rupture was recorded.

Endoscopic procedure

Endoscopy and glue application were performed in all cadavers by the same author (AEG). Cats were placed in dorsal recumbency with the head slightly elevated. The fibrin glue (TISSEEL [Fibrin Sealant]; Baxter International Inc) was thawed in a warm water bath for 5 minutes (removed from pouch, 33 to 37 °C) immediately prior to use.4,5 Tracheoscopy was performed in a routine fashion using a 4.9-mm video bronchoscope (Fujinon EB-270S; Fujifilm Medical Systems USA, Inc) with a working channel of 2 mm to allow passage of a double lumen catheter (Duplocath 180; Baxter International Inc). After identification of the tracheal laceration, any mucus or fluid surrounding the defect was suctioned. The tracheal laceration length was measured using incorporated centimeter markings on the endoscope insertion tube. The fibrin glue was applied to the tracheal defect using a double lumen catheter inserted through the working channel of the endoscope as described below. The glue components were given 2 minutes to achieve adequate polymerization. After application of the fibrin glue, contact with the tip of the catheter or endoscope was avoided, and suction was not used in this area to prevent aspiration or displacement of the clot.

Phase I

For cats in treatment group 1, fibrin glue was applied in a bridging fashion across the luminal edges of the tracheal defect until the entire defect was covered (Figure 1).

Figure 1
Figure 1

Illustration of endoscopically applied fibrin glue to bridge (A) or fill (B) postintubation tracheal lacerations induced in cadaveric cats (10 fresh cadavers within 12 hours of unrelated euthanasia and 10 frozen cadavers allowed to thaw at room temperature for 48 hours) with the illustrations depicting cats in dorsal recumbency, and the ventral aspect of the trachea (arrowhead) toward the top of the image.

Citation: American Journal of Veterinary Research 84, 3; 10.2460/ajvr.22.08.0137

Phase II

After analyzing the results of phase I and determining that the fibrin glue showed no success when used in a bridging manner, the gluing technique was modified. For cats in treatment group 2, the catheter was advanced through the tracheal laceration, and the fibrin glue was instilled into the peritracheal gap created by the defect until the glue filled the gap and extended into the tracheal lumen for the full length of the defect working caudal to cranial and deep to superficial.

Leak testing

The airway of each cat was exposed via median sternotomy and separation of the ventral cervical musculature. Leak testing was performed by either submersion in a sterile saline bath or by direct observation of mediastinal ballooning. An endotracheal tube was placed at the level of the larynx with the cuff inflated, and positive pressure ventilation was applied using a manual resuscitation bag generating approximately 22 cm H2O. A leak was defined as air bubbles released into the saline bath during positive pressure ventilation or evidence of mediastinal ballooning adjacent to the tracheal defect. Once leak testing was complete, the trachea of each cat was cut along the ventral midline to visually evaluate the quality of glue application and adherence to the trachea. For cats with evidence of air leakage, the length of the tracheal defect remaining was measured and recorded.

Statistical analysis

Length of tear (cm), location of tear, volume of fibrin glue applied (mL), procedural time (identification of tear, suctioning, glue application, and glue polymerization; minutes), fibrin glue efficacy (seal attained, yes vs no), and remaining defect (cm) were recorded and reported using descriptive statistics. Data were checked for normality using a Shapiro-Wilk normality test (GraphPad Prism version 8.0; GraphPad Software Inc.) and are reported as mean ± SD if normally distributed or median and range if not normally distributed.

Results

Twenty domestic shorthair feline cadavers, consisting of 13 females and 7 males of unknown age, were obtained following euthanasia. Both frozen (cats 1 through 10) and fresh cadavers (cats 11 through 20) were used. Treatment group 1 consisted of 11 adult female intact domestic shorthair feline cadavers; treatment group 2 consisted of 9 adult intact domestic shorthair feline cadavers (2 female, 7 male). Endotracheal cuffs were overinflated with a median air volume of 13.5 mL (range, 10 to 30 mL) to achieve a tracheal rupture (> 300 mm Hg). Experimentally induced tracheal lacerations were full thickness with a mean length of 3.27 ± 0.96 cm (95% CI, 2.85 to 3.69 cm; Supplementary Table S1). The median endotracheal tube inner diameter for treatment group 1 was 3.5 mm (range, 3.5 to 4.5 mm), while the median tube diameter for treatment group 2 was 4 mm (range, 3.5 to 5 mm). All tracheas tore at the juncture between the trachealis muscle and cartilaginous rings (Figure 2). Most tears were within the caudal cervical portion of the trachea, with 1 cat (cat 9) tearing in the cranial cervical region and 3 cats (cats 5 through 7) extending into the intrathoracic region. The overall median volume of fibrin glue endoscopically applied to the tracheal tear was 0.5 mL (range, 0.2 to 2 mL), with 0.4 mL (range, 0.2 to 1.2 mL) applied in a bridging fashion and 0.5 mL (range, 0.4 to 2 mL) applied in a filling fashion. The mean endoscopic procedural times for bridging the defect and filling the defect were 10.5 ± 4.1 minutes and 7.8 ± 1.5 minutes, respectively.

Figure 2
Figure 2
Figure 2

Representative endoscopic images of cadaveric cat tracheas before (A; cat 1) and after (B; cat 13) endoscopic application of fibrin glue to fill postintubation tracheal lacerations during the study described in Figure 1. In both images, dorsal (D) is toward the bottom and ventral (V) is toward the top.

Citation: American Journal of Veterinary Research 84, 3; 10.2460/ajvr.22.08.0137

Treatment group 1 had no success in attaining a seal using the bridging technique. A complete seal was obtained in 6 of the 9 fresh cadavers when complete filling of the defect with fibrin glue was performed (treatment group 2; Figure 3). In the remaining 3 fresh cadavers, air leakage was restricted to the dorsal mediastinum with no evidence of lateral mediastinal ballooning; the subjective lifting of the trachea upon positive ventilation was suggestive of dorsal mediastinal ballooning (cats 14, 19, and 20). Upon visual examination of the remaining tracheal defects after failed leak testing (n = 14 examined), a partial seal was obtained in all cats, and the defect was shorter in length than the original tear (1.2 ± 0.7 cm; 95% CI, 0.8 to 1.7 cm; 5 defects were not measured). As there was sufficient glue coverage in all cases, remaining defects were identified as a lack of adherence of the fibrin clot to the luminal edges.

Figure 3
Figure 3

Representative image showing gross visual inspection of the fibrin glue clot filling the 4.5 cm post­intubation tracheal lacerations of cadaveric cat 15 of the study described in Figure 1. The cat is in dorsal recumbency, and the cat’s head is toward the left of the image.

Citation: American Journal of Veterinary Research 84, 3; 10.2460/ajvr.22.08.0137

Discussion

The results of this study suggest that endoscopically delivered fibrin is a feasible method for sealing experimentally induced tracheal lacerations in cadaver cats when instilled into the defect (filling method) rather than used in a bridging method. In addition, the procedure was easy to perform with routinely available endoscopic equipment.

The fibrin sealant used in this study was made from pooled human plasma, containing sealer protein and thrombin components.6 The sealer protein includes fibrinogen, as well as synthetic aprotinin, a fibrinolysis inhibitor. When expelled from a double-chamber syringe and allowed to mix, the thrombin converts fibrinogen to fibrin, forming a fibrin clot. Together, these components mimic the final stage of the blood coagulation cascade. Complications in humans have been reported due to the presence of the antifibrinolytic aprotinin, which has been shown to be associated with anaphylactic reactions.7 Additionally, air embolisms have occurred with the use of spray devices employing a pressure regulator at higher than recommended pressures in people.8

Fibrin glue is approved for use during surgery to aid with standard methods of hemostasis, to be a tissue sealant, and to support wound healing.9,10 Indications include abdominal, cardiovascular, orthopedic, and thoracic surgeries, and urology procedures.1115 Treatment of PITL in people with fibrin glue has been reported with success being attributed to patient selection.4 Good candidates for the endoscopic application of fibrin glue include patients that are stable, spontaneously breathing, and not experiencing any esophageal injury, pneumomediastinum, emphysema, or infection. In addition, the tracheal laceration must be ≤ 4 cm in length.4 Research regarding PITL in humans has led to the development and use of a grading system.4,5 Levels I, II, and IIIA describe lesions that do not involve esophageal injury or mediastinitis but differ in degree of involvement of the tracheal mucosa and submucosa. A level IIIA lesion is defined as a full-thickness tear in the cervical trachea. Level IIIB is defined as a laceration of the tracheal wall severe enough to cause esophageal injury or mediastinitis. Level IIIB lesions must be managed with surgical repair.5 Conservative management is recommended for Levels I to IIIA, which includes endoscopic application of fibrin glue.5 If categorized, all cats in this study would have presented with level IIIA lacerations, justifying the use of fibrin glue as a treatment method. In this study, all cats sustained full-thickness tears, likely due to the tear induction method used.

Fibrin sealants have been used both clinically and experimentally in dogs and cats.1623 Applications in dogs include the treatment of an aural hematoma, reduction of experimentally induced pulmonary air leak, and as an adjuvant to traditional suturing of esophagogastric anastomoses, tracheal anastomoses, and cutaneous wounds.16,1820,24 In dogs with experimentally induced tracheal transections, anastomoses supplemented with fibrin sealant allowed for minimal suture use and facilitated healing with unimpaired ventilation and no air leakage.24 Applications in cats include using fibrin glue for allograft fusions and neuro- and orthopedic surgical procedures, such as the repair of cranial nerves and to help seal mucosa overlying exposed mandibular plates.2124 Using human-based fibrin glue in other animal species has the potential to cause cross-species reactivity. However, there have been no reported adverse events associated with its use in cats or dogs.16,1823 Furthermore, while enough sealant needs to be applied to ensure that the area is adequately covered, complications can arise from using excess glue, as this does not allow for proper healing of the underlying tissues.25 However, no adverse effects were observed with large amounts of fibrin glue used to close tracheal anastomoses in dogs.24

During leak testing, ventilation was performed with positive pressure via a manual resuscitation bag. Spontaneous breathing in a live animal employs negative pressure, which generates pleural pressures between −2 and −6 cm H2O.26 Positive pressure ventilation can create airway pressures of 15 to 20 cm H2O, which may have influenced glue stability.27 Additionally, any extra flexion of the neck could cause the fibrin clot to dislodge, causing a leak. However, research using fibrin glue on dogs for tracheal anastomoses showed no dislodgement from flexion or extension of the neck.24 Furthermore, in this study, each glue application was allowed 2 to 5 minutes to achieve complete polymerization prior to leak testing. In a clinical setting, the cat will either be spontaneously ventilating (low pressure) or mechanically ventilating (high pressure), which could cause movement of the clot during this time frame. However, the glue reaches 70% tensile strength after 10 minutes and continues to increase in tensile strength over the course of 2 hours.24 Therefore, it is possible that additional time would allow for improved sealing of tissues in live or cadaver cats.

Cats 1 through 10 were frozen and thawed prior to the procedure and kept refrigerated after the procedure, prior to leak testing. This methodology resulted in a substantial amount of fluid and blood pooling within the trachea that was difficult to suction fully. It is possible that the freezing, thawing, and cooling processes used on these cats did not allow the fibrin glue to properly bind to the tracheal tissue, resulting in the failure of a seal. The lack of natural fibrinogen and thrombin in cadavers due to degradation of tissues likely contributes to the lack of adherence as well. Because of the concern for the methods contributing to the lack of attaining an adequate seal, cats 11 through 20 were obtained within 12 hours of euthanasia. For cats 1 through 11, the glue was placed across the defect in a bridging fashion. Cat 11 (fresh cadaver) also had glue applied in a bridging fashion, and when leak testing was unsuccessful, glue application was adjusted to filling of the defect. It is difficult to extrapolate the potential success rate of bridging the defect if applied to additional fresh cadavers. Following our change in technique, cats 12 through 20 showed little to no mediastinal ballooning during leak testing. While a complete seal was attained in only 6 of the 9 cats, fibrin glue would likely be more effective on live tissues with endogenous hemostatic properties. Furthermore, in all cases in which a leak was observed, the remaining defect was not due to a lack of glue coverage but a lack of adherence of glue to the luminal edges. Additionally, the length of the defect was smaller than the original defect in all measured cases. Therefore, in clinical cases, signs may be improved despite not obtaining a complete seal.

Evidence to support using fibrin glue as a treatment for PITL in cats would benefit from future evaluation of fibrin glue in clinical cases presenting with a tracheal laceration. A study of this nature would remove variables concerning glue interaction with cadaveric tissues. In summary, endoscopic application of fibrin glue may be a feasible treatment for PITL in cats. Fibrin glue could be a potential minimally invasive treatment alternative to prolonged conservative management and invasive surgical procedures in veterinary practice.

Supplementary Materials

Supplementary materials are posted online at the journal website: avmajournals.avma.org

Acknowledgments

The authors thank Tom DeHaan for obtaining and transporting the specimens necessary for conducting this research.

This research was supported by the Linda F. Hayward Florida Veterinary Scholars Program and the University of Florida College of Veterinary Medicine. The authors declare that there were no conflicts of interest. Funding sources did not have any involvement in the study design, data analysis and interpretation, or writing and publication of the manuscript.

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Supplementary Materials

  • Figure 1

    Illustration of endoscopically applied fibrin glue to bridge (A) or fill (B) postintubation tracheal lacerations induced in cadaveric cats (10 fresh cadavers within 12 hours of unrelated euthanasia and 10 frozen cadavers allowed to thaw at room temperature for 48 hours) with the illustrations depicting cats in dorsal recumbency, and the ventral aspect of the trachea (arrowhead) toward the top of the image.

  • Figure 2

    Representative endoscopic images of cadaveric cat tracheas before (A; cat 1) and after (B; cat 13) endoscopic application of fibrin glue to fill postintubation tracheal lacerations during the study described in Figure 1. In both images, dorsal (D) is toward the bottom and ventral (V) is toward the top.

  • Figure 3

    Representative image showing gross visual inspection of the fibrin glue clot filling the 4.5 cm post­intubation tracheal lacerations of cadaveric cat 15 of the study described in Figure 1. The cat is in dorsal recumbency, and the cat’s head is toward the left of the image.

  • 1.

    Mitchell SL, McCarthy R, Rudloff E, Pernell RT. Tracheal rupture associated with intubation in cats: 20 cases (1996–1998). J Am Vet Med Assoc. 2000;216(10):15921595. doi:10.2460/javma.2000.216.1592

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Hardie E, Spodnick G, Gilson S, Benson J, Hawkins E. Tracheal rupture in cats: 16 cases (1983–1998). J Am Vet Med Assoc. 1999;214(4):508512.

  • 3.

    Lawrence D, Lang J, Culvenor J, Mischol G, Haynes S, Swinney G. Intrathoracic tracheal rupture. J Feline Med Surg. 1999;1(1):4351. doi:10.1016/S1098-612X(99)90009-8

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Fiorelli A, Cascone R, Di Natale D, et al. Endoscopic treatment with fibrin glue of post-intubation tracheal laceration. J Vis Surg. 2017;3:102.

  • 5.

    Cardillo G, Carbone L, Carleo F, et al. Tracheal lacerations after endotracheal intubation: a proposed morphological classification to guide non-surgical treatment. Eur J Cardiothorac Surg. 2010;37(3):581587.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Redl H, Schlag G. Fibrin sealant and its modes of application. In: Redl H, Schlag G (eds). Fibrin Sealant in Operative Medicine. Springer; 1986:1326.

    • Search Google Scholar
    • Export Citation
  • 7.

    Dietrich W, Späth P, Ebell A, Richter J. Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight reexposures to aprotinin in heart operations. J Thorac Cardiovasc Surg. 1997;113(1):194201. doi:10.1016/S0022-5223(97)70415-X

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Ebner F, Paul A, Peters J, Hartmann M. Venous air embolism and intracardiac thrombus after pressurized fibrin glue during liver surgery. Br J Anaesth. 2011;106(2):180182.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Mankad PS. The role of fibrin sealants in hemostasis. Am J Surg. 2001;182(2):S21S28.

  • 10.

    Dunn CJ, Goa KL. Fibrin sealant. Drugs. 1999;58(5):863886. doi:10.2165/00003495-199958050-00010

  • 11.

    Vecsey D. New method of hemostasis with adhesives in adenomectomy. Z Urol Nephrol. 1980;73(1):5762.

  • 12.

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