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Combination Therapy With Intrapleural Doxycycline and Talc in Reduced Doses Is Effective in Producing Pleurodesis in Rabbits^*

^* From the Pulmonary Division (Drs. Dikensoy, Zhu, and Light), St. Thomas Hospital, Nashville, TN; and Division of Allergy, Critical Care and Pulmonary Disease (Drs. Stathopoulos and Lane) and Department of Radiology and Radiological Sciences (Dr. Donnelly), Vanderbilt University Nashville, TN.

Correspondence to: Richard W. Light, MD, FCCP, Director of Pulmonary Disease Program, St. Thomas Hospital, 4220 Harding Rd, Nashville, TN 37205; e-mail: RLIGHT98{at}yahoo.com

Background: It has been suggested that talc and doxycycline might be acting through different pathways in creating pleurodesis. We hypothesized that combining doxycycline and talc in half the usual doses would be synergistic in inducing pleurodesis.

Methods: Thirty-two rabbits were equally allocated into four groups: group 1, half-dose combination (5 mg/kg of doxycycline and 200 mg/kg of talc slurry); group 2, quarter-dose combination (2.5 mg/kg of doxycycline and 100 mg/kg of talc slurry); group 3, half-dose doxycycline (5 mg/kg of doxycycline); and group 4, half-dose talc (100 mg/kg of talc slurry). The pleurodesis scores from historical groups that received a full dose of talc (400 mg/kg) or doxycycline (10 mg/kg) were also compared to those obtained in the current study. Pleural fluid lactate dehydrogenase and protein levels were measured 24 h after the injection. Pleurodesis was graded from 1 (none) to 8 (> 50% symphysis) by two observers blinded to treatment groups. All rabbits underwent an ultrasonic examination on each side of their chest for the evaluation of pleurodesis.

Results: The mean pleurodesis score in the half-dose combination group was significantly higher than that in the half-dose talc group, half-dose doxycycline group, and the historical full-dose talc group (p = 0.009, p = 0.01, and p < 0.05, respectively). The quarter-dose combination group also had a significantly higher mean pleurodesis score compared to the half-dose talc group (p = 0.013). The difference between the historical full-dose doxycycline and the half-dose combination or quarter-dose combination groups was not significant (p > 0.05). A significantly positive correlation existed between the pleurodesis score and the ultrasound scores (r = 0.876, p = 0.000000005).

Conclusions: This study demonstrates that the combination of half doses of talc and doxycycline is more effective than the half dose of either drug alone or the full dose of talc in producing pleurodesis in rabbits. In addition, ultrasound is an accurate imaging modality for the evaluation of pleurodesis, in that the absence of pleural gliding on ultrasound correlates well with the presence of a pleurodesis in rabbits.

Key Words: combination • doxycycline • pleural effusion • talc • ultrasound