As adjuncts to suturing or stapling, various surgical sealants have been developed and progressively practised in treating AAL in the last decade. According to a survey of European Association for Cardio-Thoracic Surgery and European Society of Thoracic Surgeons, more than 60% of surgeons used sealants in the practice routinely or when indicated . However, the sealant use was mostly not based on clinical evidence. This is believed to be due to inconsistent data of the published clinical trials assessing the sealing efficacy of surgical sealants. In the current Cochrane review including a total of 16 randomized controlled clinical trials investigating the sealants for preventing air leaks after pulmonary resections, only three trials demonstrated a significant reduction in the length of hospital stay in the treatment group . Post-operative chest tube time was significantly reduced in treatment group only in three trails. Significant difference in duration of air leaks was only found in six out of twelve clinical trails. Aside from some design flaws of these studies, length of hospital stay and duration of chest tube are inadequate primary endpoints to examine the sealant’s efficacy, as they are determined not only by AAL, but also by various other factors including relevant co-morbidities, inadequate post-operative pain control, prolonged fluid output. In contrast, the in vitro lung model in the present study provides a reliable means to assess AAL quantitatively and is able to test the burst pressure of sealant. Furthermore, the elasticity of sealant has also been evaluated. More clinical relevance could be found to compare the sealing efficacy of different sealants in treating AAL with this in vitro model.
TP is a novel, fully synthetic, self-adhesive sealant patch, which is biodegradable. It consists of TissueBond as an adhesive polymer, PLGA and methylene blue. Since the first launch in 2007, the original product, TissuePatch3TM has been progressively widespread as an adjunct to seal leakage of air, chylous fluid and blood in lung surgery, thyroidectomy, major neck surgery as well as in the prevention of cerebrospinal fluid leaks following neurosurgery. In the present study, we demonstrated the strong sealing efficacy of TP as the new generation product under mechanical ventilation. The mean burst pressure exceeded the upper limit of the inspiratory pressure, which is typical in most clinical settings (Pmax ≤ 40 mBar). In the present experiment, certain variation in the size of ventilated lower lobes could not be totally avoided. However, we did not observe remarkable difference in this regard during the tests. It could be explained that the lungs were harvested from the pigs in almost the same weight (around 80 kg). In all tests, the lower lobe was fully inflated when TVi was 400 ml or higher, indicating the absence of significant difference in the size of lower lobes.
In a recent in vitro experiment comparing the sealing efficacy of six different sealants including TissuePatchDuralTM (TPD, Tissuemed Ltd, Leeds, UK) similar to TissuePatchTM, Pedersen et al. fixed harvested porcine lungs in a Plexiglas chamber filled with isotonic saline . After sealant application on deflated lungs, the lungs were ventilated with incremental peak airway pressure and air leaks were assessed by visual inspection of air bubbles in submersion tests. Their results demonstrated a very low median burst pressure of TPD (25 mBar). The sealant never withstood peak pressures higher than 30 mBar. Compared to the in vitro model of the present experiment, certain factors may have biased their study to the disadvantage of TPD. Firstly, the TPD film was applied to deflated lungs, whereas the manufacturer recommends that the lung should be ¾ inflated during application. The subsequent lung re-inflation and stretching may have deteriorated the bonding between the adhesive polymer and lung surface due to break of the cross-links. Furthermore, the time from lung harvest to experimentation averaged as long as 24 hours. The resulted protein degradation may also have impaired the cross-linking of polymer at lung tissue, resulting in weaker sealing efficacy. Additionally, air leakage assessment was performed via inspection of air bubbles, and observer blinding was not possible due to the obvious differences in product appearance in their experiment.
Our results are comparable to the previously published data of fibrin sealant patches in in vivo animal experiments. In experimental studies with beagles, the working group of Dr. Kawamura and Dr. Gika made defects on the lung surface (5 × 10 mm and 5 × 20 mm, respectively) and evaluated the sealing effect of fibrin glue against air leakage with different methods of application. In the group using collagen fleece, coated with fibrinogen and thrombin (TachoComb®, ZLB Behring Co., King of Prussia, PA, USA), the mean seal breaking pressure was as high as 36 ± 6 mBar and slightly over 40 mBar, respectively [12, 13].
TP is a ready to use sealant, which does not require any preparation before application. It bonds to surgical site in 60 seconds. Compared to TP, fibrin patches such as TachoComb® or TachoSil® (Takeda, Zurich, Switzerland) need to be moistened before application, with pressure required for 3 to 5 minutes after application according to the usage guide. Furthermore, fibrin sealants are typically derived from human or bovine blood plasma, exposing patients to the potential risk of transmission of blood-borne diseases [5, 12]. Kamamura et al. reported infection of human parvovirus B19 in more than 20% of patients following use of fibrin sealant during lung resection . In this respect, application of TP as a fully synthetic, biodegradable material completely eliminates this risk. As a further advantage, TP can be delivered thoracoscopically by means of a dedicated delivery system. Nevertheless, it is of utmost importance in confirming the clinical benefits of TP by means of prospective, randomised controlled clinical trials.