Ann Thorac Surg 1995;59:825-827
© 1995 The Society of Thoracic Surgeons
Resolution of Experimental Pneumothorax in Rabbits by Oxygen Therapy
Ronald C. Hill, MD,
Donald P. DeCarlo, Jr, BS,
Jeffrey F. Hill,
Kathryn C. Beamer, MS,
Mandy L. Hill,
Gregory A. Timberlake, MD
Section of Cardiovascular and Thoracic Surgery, Department of Surgery, West Virginia University School of Medicine, Morgantown, West Virginia
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Abstract
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The treatment of asymptomatic patients with small pneumothoraces (ie, less than 20% by volume) has included observation, tube thoracostomy, and operation. When observation is used, the anticipated expansion of the lung has been estimated to be 1.25% of the lung volume daily. This study was designed to evaluate the use of inhaled oxygen as a method to accelerate the resolution of a pneumothorax in a rabbit model. Experimental pneumothoraces were created in 23 white New Zealand rabbits. Group 1 (9 rabbits) were placed in a cage with room air and group 2 (11 rabbits) were placed in a cage with high oxygen concentration. Three rabbits died before completion of the study. Serial chest roentgenograms were performed until the pneumothoraces resolved. The majority of rabbits treated with oxygen had resolution of their pneumothoraces by 36 hours, whereas the majority of rabbits treated with room air did not show complete resolution before 48 hours. Biopsies showed no evidence of damage secondary to oxygen treatment. Oxygen treatment was found to be significantly better in the early resolution of pneumothoraces when compared with room air. This establishes an alternative treatment for some pneumothoraces that are small and asymptomatic.
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Introduction
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See also page 827.
The etiology of pneumothorax includes spontaneous, iatrogenic, traumatic, and intrinsic lung disease, as well as connective tissue disorders and endometriosis [1]. Nonoperative treatment in asymptomatic patients with less than 20% pneumothoraces by volume has included observation and tube thoracostomy with or without the instillation of sclerosing agents [2]. Operative management has included surgical pleurodesis, as well as pleurectomy [2]. When conservative treatment has been employed, the anticipated expansion of the lung is approximately 1.25% of the lung volume daily [1, 3]. It is suggested in the literature that oxygen may speed resolution of the pneumothorax by increasing the gradient for nitrogen absorption, but this has not been documented [1]. The purpose of this study was to determine whether inhaled oxygen would cause accelerated resolution of an experimental pneumothorax in the rabbit model.
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Material and Methods
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Twenty-three white New Zealand rabbits, weighing 2.3 to 3.5 kg, were anesthetized with 44 mg/kg ketamine and 5 mg/kg xylazine. Roentgenography of each rabbit was performed using a General Electric mobile x-ray unit (General Electric, Pittsburgh, PA) at the settings of 10 mA, 75 kV, at 1 second. After the documentation of a normal rabbit chest roentgenogram, a stab incision was made 1 cm below the right or left scapular tip through which a sterile 16-gauge, 5-cm (2-inch) plastic catheter was inserted into the pleural space. A sterile syringe was attached to the catheter and, after aspiration to rule out pulmonary or vascular injury, 20 mL of room air was injected into the pleural space creating a complete (100%) pneumothorax. The syringe was removed so pressure equilibration could occur, thus preventing a tension pneumothorax. Roentgenography of each rabbit was performed to confirm complete pneumothoraces, after which the rabbits were divided into two groups. Group 1 (9 rabbits) were placed in a cage with room air (oxygen concentration = 21%) and group 2 (11 rabbits) were placed in a cage with high oxygen concentration (oxygen concentration = 60%). The Plexiglas containers that housed the rabbits had approximately eight holes, 1 cm in diameter, so that equilibration of gases (ie, carbon dioxide and oxygen) could occur. Oxygen was transmitted to the cages from the wall outlet by tubing, which then was attached to the cage to prevent dislodgment. Roentgenography of each rabbit was performed three times a day until the pneumothoraces resolved. Three rabbits that died before completion of the study underwent immediate autopsy.
The oxygen concentration within both groups was analyzed using a 406 oxygen analyzer (Instrumentation Laboratory, Lexington, Massachusetts). By taking samples of air from various locations within the cage, an average oxygen concentration was obtained. The oxygen concentration within the intrapleural space of one rabbit was measured by securing a catheter in the space and attaching the oxygen monitor. After baseline room air readings, the oxygen concentrations within the pleural space were recorded after 20 minutes of high oxygen exposure. The lungs of four additional rabbits, two exposed to room air and two exposed to an oxygen concentration of 60% for 36 hours, were examined by electron microscopy for evidence of oxygen-related changes. All animals received humane care in compliance with the ``Guide for the Care and Use of Laboratory Animals,'' published by the National Institutes of Health (NIH publication 85-23, revised 1985).
The surface area of the intrapleural space was measured on each roentgenogram using a personal computer imaging system with Optimas software (Optimas Corp, Edmonds, WA). The data, consisting of the area of the pneumothorax determined by the computer imaging system for each roentgenogram, were recorded and plotted as regression curves. Regression correlation coefficients were analyzed statistically using STAT EXACT [4].
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Results
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The results are shown in Figure 1
. Of the rabbits (group 2) exposed to an oxygen concentration of 60%, 2 had resolution of their pneumothorax within 12 hours, 6 demonstrated complete resolution at 24 hours, and 3 had complete resolution within 36 hours.
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Fig 1. . Rate of resolution of pneumothoraces in rabbits treated with room air (oxygen concentration = 21%) and high oxygen concentration (60%).
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Although 2 rabbits treated with room air (group I) had resolution by 24 hours, 7 took longer than 48 hours to reach complete resolution. The average for 6 of the rabbits in the control group was 60.2 hours, and 2 rabbits did not resolve until 77.5 and 101.8 hours.
As can be seen in Figure 2, quadratic regression lines for group 1 (room air) and group 2 (60% oxygen) were plotted. Statistical analysis demonstrated significant differences (p < 0.001, 
2 = 0.003).
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Fig 2. . Regression curves showing a significant difference between the rate of resolution of pneumothoraces in rabbits treated with an oxygen concentration of 60% versus those treated with an oxygen concentration of 21%.
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Three rabbits died before completing the study. Causes of death included a punctured small intestine, bleeding, and a lethal injection of the anesthetic drugs.
Four additional rabbits without pneumothoraces underwent room air and oxygen exposure for the same time period as the study rabbits. In reviewing the histologic sections, no damage due to high oxygen concentration was seen by electron microscopy, as compared with the room air controls.
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Comment
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Spontaneous pneumothorax originally was described by Itard in 1803 and recognized as a pathologic process involving emphysematous blebs by Laennec in 1819 [5, 6]. Since these descriptions, nonoperative and operative surgical treatments subsequently have evolved.
Nonoperative treatment includes observation, small tube or catheter aspiration for 1 to 2 hours followed by its removal and observation, and standard tube thoracostomy [2, 7]. Operative management entails surgical pleurodesis with resection or oversewing of blebs, usually in the apex, and pleurectomy [2, 3]. On occasion, patients may refuse surgical procedures and indeed may refuse placement of chest tubes. Subsequently, observation becomes the treatment modality, relying on the pleural surface to reabsorb the intrapleural air. Also, a residual pneumothorax may be present on the chest roentgenogram after the removal of chest tubes, which may be treated with observation as well. Air (oxygen concentration of 21%) is reabsorbed daily from the pleural space at a rate of 1.25% of its volume [1, 3, 5]. Some authors suggest that the administration of oxygen may facilitate resolution of the pneumothorax [1, 3, 5] by increasing the nitrogen gradient. Although this method is used clinically on occasion, laboratory studies correlating with these clinical findings are lacking in the literature.
This study evaluated the role of inspired oxygen at a concentration of 60% in the resolution of a nontension pneumothorax. Rabbits were anesthetized and a complete pneumothorax created and equilibrated so that tension was obviated. They were divided into two groups. Group 1 was treated with room air (oxygen concentration = 21%) and group 2 with a high inspired oxygen concentration (60%). The rabbits in the high oxygen environment reexpanded their lungs within 24--36 hours, whereas those rabbits in room air averaged a much slower rate. The equilibration of the oxygen in the cage and pleural space was within 20 minutes.
Nitrogen was not measured in this study. However, one explanation that has been suggested is that oxygen may accelerate the resolution of a pneumothorax by increasing the gradient for nitrogen absorption, as suggested by Bojar and Kittle [1].
In conclusion, we have evaluated the use of oxygen in the rabbit model to facilitate the resolution of pneumothoraces. Although we resolved 100% pneumothoraces in rabbits, this modality is not recommended for anything more than 15% to 20% collapse in patients whose pneumothoraces are managed by observation only. Future studies in our laboratory will explore using lower concentrations of oxygen to try to define the minimal effective oxygen concentration. We believe that this study confirms our clinical observations and shows that oxygen therapy is a way of accelerating pneumothorax resolution when observation is used in the asymptomatic patient.
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Acknowledgments
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We thank Edwin Towsend, PhD, for statistical analysis, Nathan Rodman, MD, for pathological review, and Ms Balinda Schwartz for her assistance in the preparation of the manuscript.
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Footnotes
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Presented at the Forty-first Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 10--12, 1994.
Address reprint requests to Dr Hill, Department of Surgery, West Virginia University School of Medicine, Box 9238, Morgantown, WV 26506-9238.
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References
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- Bojar RM, Kittle CF. The surgical management of recurrent or persistent pneumothorax: pleurectomy. In: Kittle CF, ed. Current controversies in thoracic surgery. Philadelphia: Saunders, 1986:51--7.
- Hill RC. The pleura and empyema. In: Sabiston DC Jr, Lyerly HK, eds. Essentials of surgery. Philadelphia: Saunders, 1994:603--5.
- Kirchner LT, Swartzel RL. Spontaneous pneumothorax and its treatment. JAMA 1954;155:24–9.
- Mehta CR, Patel NR. A network algorithm for performing Fisher's exact test in vac contingency tables. J Am Stat Assoc 1983;78:427–34.
- DeVries WC, Wolfe WG. The management of spontaneous pneumothorax and bullous emphysema. Surg Clin North Am 1980;60:851–66.[Medline]
- Gobbel WG Jr, Rhea WG Jr, Nelson IA, Daniel RA Jr. Spontaneous pneumothorax. J Thorac Cardiovasc Surg 1963;46:331–44.
- Hood RM. Techniques in general thoracic surgery. Philadelphia: Lea & Febiger, 1993:157--60.
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Ann. Thorac. Surg. 1995 59: 827-828.
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