Can tissue adhesives and glues significantly reduce the incidence and length of postoperative air leaks in patients having lung resections?

July 24, 2007

October 17, 2007

Jeymi Tambiah, Randolph Rawlins, Daniel Robb and Tom Treasure, Specialist Registrars in Cardiothoracic Surgery (Department of Thoracic Surgery, Guy's Hospital, St. Thomas's Street, London, UK)

Joel Dunning, Department of Thoracic Surgery, Guy's Hospital, St. Thomas's Street, London, UK

In [adult patients undergoing lung resection], does [intraoperative use of surgical adhesives] reduce the [incidence and length of postoperative air leaks]?

You have just completed a right upper lobectomy in a 67 year old smoker for non-small cell carcinoma. He had multiple adhesions and an incomplete fissure and on testing there were many air leaks. A colleague has been trying out a spray-on glue to reduce air leaks and thus you ask for this glue to be brought into theatre and apply it liberally. The air leak stops on day one, the drains are all removed on day 3 and he is discharged on day 5. You wonder whether you should use this glue for all your lobectomy patients and thus resolve to look this up in the literature.

Medline 1950 to Jan 2007 using the OVID interface

[exp lung neoplasms/ OR lung neoplasm.mp/ OR lung carcinoma.mp OR lung cancer.mp OR pneumonectom$.mp OR lobectom$.mp OR lung resection.mp OR pulmonary resection$.mp OR Thoracotom$.mp] AND [exp Tissue Adhesives/ OR tissue adhesive.mp OR exp Fibrin Tissue Adhesive/ OR sealant.mp OR vivostat.mp OR fibrin glu$.mp OR TachoComb.mp OR bioglue.mp OR focalseal.mp]

A total of 261 papers were identified using the reported search of which 12 represented best evidence on the subject. These studies are summarised below

A total of 12 papers (11 trials and 1 systematic review) have been cited in the comparison table. Apart from Tansley et al, all were included in the comprehensive Cochrane Systematic Review written by Serra-Mitjans et al. Most trials looked at 3 primary outcomes: Air Leak duration, Length of time of intercostal drainage, Length of hospital stay. 7 trials use fibrin based sealants, 3 trials use polyethylene- glycol based sealants, and 1 trial uses a glutaraldehyde based sealant.

The basic conclusions are: 6 trials found a significant reduction in the duration of air leak after use of a sealant as compared to controls[Tansley,Porte, Wain, Lang, Fabian, Belboul], however 5 trials found the difference to be non-significant[Allen, Macchiarini, Wong, Mouritzen, Fleisher].

Only 2 trials found a significant reduction in the time of intercostal drainage compared to controls[Tansley, Fabian] , 6 trials found the difference to be non-significant[Wain, Belboul, Allen, Wong, Fleisher].

Only 2 trials found length of hospital stay to be significantly shorter in groups treated with sealant compared to their controls[Tansley, Allen], whilst 7 trials found a non-significant difference[Porte, Wain, Fabian, Belboul, Macchiarini, Wain, Fleisher].

We conclude that there is weak evidence that sealants may reduce the duration of air leaks following lung resection surgery but it is unlikely their use influences the length of time of intercostal drainage or length of hospital stay for the patient.

However there are several points which need clarification when looking at these trials in detail. Further work will be needed to answer the question definitively. Some of the issues which need addressing are as follows:

1. The outcome measures. The majority of trials did not define management of intercostal drains post-operatively. This is highly variable between institutions. Also blinding of observers post-operatively was not always clearly stated. Therefore using time of drainage as an outcome measure and subsequently length of hospital stay as another primary outcome measure (as this must depend on time of drainage) seems flawed. The only definitive outcome measure which can be reliably used when comparing results between studies is post-operative air leak duration.

2. The sealant properties. There were 7 trials using fibrin based sealants, 3 trials using polyethylene- glycol based sealants and one trial using a glutaraldehyde based sealant. Of the 7 studies using fibrin based sealants, post-operative air leak duration was significantly reduced in 3 trials but made no difference in the remaining 4. Of the 3 studies using polyethylene-glycol based sealants, 2 found a significant reduction in post-operative air leak duration compared to a single trial which found it made no difference. The single trial using a glutaraldehyde based sealant found a significant reduction in post-operative air leak duration it its treatment group as opposed to its controls. Therefore the type of sealant used will influence the results. More work needs to be performed to define this more clearly.

3. The mode of application of sealants e.g. sprays vs. syringe 'spot' application

Practicalities of usage have to be considered. E.g. light wands, autologous blood, collagen fleece, time added to surgery etc.
General problems with the set up of these trials, e.g. learning curve/ experience of surgeon; single vs. multicentre studies; no. of patients recruited etc.

We conclude that 6 of the identified randomized trials found a significant reduction in air leak duration, but 5 found no significant difference. In contrast to significant reductions in air leak, only 2 studies identified a reduction in time to chest drain removal. Also only 2 studies found a significant reduction in length of stay. There are multiple issues surrounding these studies ranging from identifying the optimal glue and delivery system, dealing with the learning curve of surgeons and robust protocols for chest drain removal to selection of patients suitable for surgical adhesive usage. Thus routine usage of surgical adhesive for all operations cannot yet be recommended, although there is a wide range of adhesives available to surgeons which may be useful in selected situations.

1. Tansley P, Al-Mulhim F, Lim E, Ladas G, Goldstraw P.. A prospective, randomized, controlled trial of the effectiveness of BioGlue in treating alveolar air leaks.
2. Serra-Mitjans M, Belda-Sanchis J, Rami-Porta R.. Surgical sealant for preventing air leaks after pulmonary resections in patients with lung cancer.[update of Cochrane Database Syst Rev. 2001;(4):CD003051; PMID: 11687173]. [Review]
3. Porte HL, Jany T, Akkad R, Conti M, Gillet PA, Guidat A, Wurtz AJ.. Randomized controlled trial of a synthetic sealant for preventing alveolar air leaks after lobectomy.
4. Wain JC, Kaiser LR, Johnstone DW, Yang SC, Wright CD, Friedberg JS, Feins RH, Heitmiller RF, Mathisen DJ, Selwyn MR.. Trial of a novel synthetic sealant in preventing air leaks after lung resection.
5. Lang G, Csekeo A, Stamatis G, Lampl L, Hagman L, Marta GM, Mueller MR, Klepetko W.. Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.
6. Fabian T, Federico JA, Ponn RB.. Fibrin glue in pulmonary resection: a prospective, randomized, blinded study.
7. Belboul A, Dernevik L, Aljassim O, Skrbic B, Radberg G, Roberts D.. The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study.
8. Allen MS, Wood DE, Hawkinson RW, Harpole DH, McKenna RJ, Walsh GL, Vallieres E, Miller DL, Nichols FC, III, Smythe WR, Davis RD, Group MSSS.. Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.
9. Macchiarini P, Wain J, Almy S, Dartevelle P.. Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations.
10. Wong K, Goldstraw P.. Effect of fibrin glue in the reduction of postthoracotomy alveolar air leak.
11. Mouritzen C, Dromer M, Keinecke HO.. The effect of fibrin glueing to seal bronchial and alveolar leakages after pulmonary resections and decortications.
12. Fleisher AG, Evans KG, Nelems B, Finley RJ.. Effect of routine fibrin glue use on the duration of air leaks after lobectomy.