Off-label use of lung sealants: the need for evidence-based guidelines and adequate indications for use

Prolonged pulmonary air leakage remains a significant challenge in thoracic surgery, and is associated with a more complicated post-operative course. Lung sealants may provide a solution, but the evidence for their effectiveness is heterogenous and head-to-head comparisons between sealants are lacking. While there are some consensus guidelines discussing when an air leak should be treated, there are no practice guidelines and specific sealant choice is left to surgeon experience. This review addresses the evidence gaps in this field. First, an overview of previously tested sealants is provided, illustrating that several sealants may be considered off-label. For example, a polyethylene glycol spray (Coseal^®) or a human serum albumin and polyethylene glycol spray (Progel^®) are only indicated in addition to sutures or staples, limiting usability on superficial parenchymal lesions. Off-label use may be concerning due to unknown risk of adverse events, and lead to legal challenges for the prescribing physician. The role of manufacturers with regard to off-label use is discussed. To close the gap in evidence, this review provides several recommendations for evidence generation, including clinical trial design, network meta-analysis, and ex-vivo human lung testing. Until high quality evidence is available, we propose forming consensus-driven practice guidelines to support thoracic surgeons in choosing lung sealants.