Phrenic Nerve Interventions for the Prevention and Management of Prolonged Air Leak and Residual Pleural Space After Pulmonary Resection: A Structured Narrative Review

Background and Objectives: Prolonged air leak (PAL) and residual pleural space (RPS) remain frequent complications after pulmonary resection. Temporary phrenic nerve modulation has been proposed to reduce pleural cavity volume by elevating the ipsilateral hemidiaphragm. Materials and Methods: This structured narrative review searched PubMed/MEDLINE, Scopus, and Google Scholar from inception to 30 June 2026 and screened reference lists. Direct evidence was defined as human post-resection studies reporting PAL, air-leak duration, drainage duration, or RPS; shoulder-pain, interscalene-block, historical, and preclinical studies were retained only as indirect mechanistic, technical, or safety context. Randomized trials and case series were appraised using RoB 2 and the JBI case-series tool, respectively. Results: Direct clinical evidence comprises three single-center randomized trials and two small uncontrolled case series. Pharmacological blockade has demonstrated recovery after discontinuation in the available clinical studies, and cryoneuroablation trials reported recovery within 30–60 days to three months. Evidence of reversibility and clinical safety remains insufficient for historical mechanical compression, which has been associated with persistent dysfunction, and for botulinum toxin, which has not been evaluated in humans for this indication. The two cryoneuroablation trials reported discordant primary results; differences in patient risk, surgical era, and outcome measurement are hypotheses rather than established explanations. No head-to-head comparison between phrenic techniques or against established space-reduction methods is available. Conclusions: Phrenic nerve modulation is biologically plausible and clinically promising in selected research populations, but the evidence is too limited and heterogeneous to support routine use or comparative recommendations. Future multicenter trials should mandate validated PAL-risk stratification, prespecified respiratory-reserve criteria, standardized PAL/RPS outcomes, and time-to-resolution or digital air-leak measures.