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BACKGROUND: Residual postoperative pleural spaces (RPPS) are often encountered during pulmonary resection; this could adversely affect the outcome and prolong recovery. Nerve cryotherapy reduces postoperative complications and does not affect neural regeneration. However, it remains unclear whether nerve cryotherapy reduces RPPS occurrence following pulmonary resection.OBJECTIVE: To explore pathological changes in the phrenic nerve following exposure to -50℃ for various freezing times, and to explore the feasibility and efficacy of phrenic nerve cryotherapy following pulmonary resection based on animal experiment results.DESIGN, TIME AND SETTING: A comparative animal study was conducted at the Animal Experimental Center of General Hospital of Chinese PLA from January to June 2008. Based on results from the animal study, a randomized, controlled, clinical study was initiated at the Department of Thoracic Surgery of General Hospital of Chinese PLA between July 2008 and July 2009.PARTICIPANTS: A total of 160 patients undergoing lobectomy were selected at the Department of Thoracic Surgery of General Hospital of Chinese PLA from July 2008 to July 2009.METHODS: Animal experiment: 27 adult goats were randomly assigned to three groups (n = 9).The phrenic nerves were frozen at -50 ℃ for 30, 60, and 90 seconds, respectively. Clinical study: 160 patients undergoing lobectomy were randomly assigned to two groups (n = 80). In the cryoanalgesia group, patients received phrenic nerve cryotherapy; phrenic nerves were frozen above the capsula cordis for 60 seconds at -50 ℃ prior to chest closure. Patients in the control group did not receive cryotherapy.MAIN OUTCOME MEASURES: Pathological changes were observed at days 1, 30, and 60 following phrenic nerve cryotherapy. In the clinical study, RPPS incidence rate was regularly recorded. Respiratory function tests, including measured forced vital capacity and forced expiratory volume in 1 second, were regularly conducted post-surgically. The incidence of post-surgical infection complications and the average days of chest drainage and hospital stay were observed and recorded.RESULTS: Animal study: nerve damage progressively increased with prolonged freezing time at -50 ℃, and recovery time from damage gradually increased. Nerves, which were frozen for 30 and 60 seconds, recovered by 30 days, and all nerves completely recovered by 60 days. Clinical study: the RPPS incidence rate was significantly less in the cryoanalgesia group compared with the control group at 1, 5, 10, and 30 days following surgery (P＜0.05). Simultaneously, phrenic nerve cryotherapy decreased the incidence rate of RPPS and shortened the average days of chest drainage and hospital stay in patients undergoing lobectomy (P＜0.05). However, phrenic nerve cryotherapy did not affect forced vital capacity, forced expiratory volume in 1 second, and the incidence rate of post-surgical infection complications (P＞0.05).CONCLUSION: Following phrenic nerve cryotherapy in the goat at -50℃, the phrenic nerve recovered to normal by 60 days. In the clinical study, phrenic nerve cryotherapy reduced the RPPS incidence rate, had no effect on pulmonary function, shortened hospital stay in patients undergoing lobectomy, and proved to be a safe, effective method.