Table 4 Detailed evaluation of previous experimental animal studies (rats and rabbits) of pleurodesis
Agent | Study | Species | Dosage | Duration | Toxicity | Notes |
|---|---|---|---|---|---|---|
Povidone-iodine | Teixeira et al. 2013 [15] | New Zealand rabbits (2–3 kg) | 2 ml @ 2, 4 and 10% | 1, 3, 7, 14, 28 days | No adverse effects despite relatively high dosage | Macroscopic results showed progressive increase in adhesion with dosage (4 and 10%) and time (demonstrating a plateau after 7 days) |
Lashkarizadeh et al. 2019 [13] | Rats (details not understood) | 0.5 ml @ 8% | 45 days | No information | Povidone-iodine had similar effectivity with Talc. | |
Yazkan et al. 2013 [14] | Wistar-albino rats (260–320 g) | 2 ml @ 1, 2 and 4% | 30 days | Although 4% dosage demonstrated some microscopic adverse effects in the contralateral pleura, statistical significance was not present. | 2 and 4% dosage deemed to be similar in effect, and both were better than 1%. All three concentrations were deemed safe, but 2% was advised. | |
Talc | Vanucci et al. 2018 [22] | New Zealand rabbits (2.1–2.5 kg) | 2 ml @ 40 mg/kg and 200 mg/kg | 14 and 28 days | Pleural granulomas were observed with both doses in all subjects on day 14. In the 40 mg/kg group, only 40% of the subjects had granulomas on the 28th day. All 200 mg/kg recipients had granulomas on the 28th day. | Adhesion did not seem to increase with higher dosage, but somewhat increased with time (14 vs. 28 days) |
Gozubuyuk et al. 2010 [23] | Wistar-albino rats (280–320 g) | 0.5 ml @ 60 mg/kg | 72 h and 7 days | Significant alveolar edema, hemorrhage and inflammation in the acute phase (72 h) compared to tetracycline and controls. At 7 days, edema was also present at a higher frequency. | Results were compared with tetracycline, and showed that Talc caused earlier pleural proliferation and fibrosis. | |
Ahn et al. 2015 [18] | Sprague-Dawley rats (220–300 g) | 400 mg/kg (volume not reported) | 28 days | Talc particles not detected in lung parenchyma. Suggested possibility for systemic effect. | ||
Muta et al. 2011 [19] | Wistar rats (300–350 g) | 400 mg/kg (volume not reported) | 30 days | Talc particles detected in the alveoli. | ||
Refosco et al. 2004 [24] | Wistar rats (200–300 g) | 2 ml @ 100 mg/kg and 500 mg/kg | 45 days | Too few subjects to evaluate toxicity. | No remarkable differences between the two very different doses. | |
Mitchem et al. 1999 [20] | New Zealand rabbits (4 kg) | ~ 0.25 ml @ 70 mg/kg | 30 days | Histological changes in the contralateral lung and blood chemistry changes. Suggested systemic adverse effect. | Although adverse effects were observed, authors concluded Talc was safer than doxycycline (other group). | |
Autologous Blood | Ozpolat et al. 2010 [16] | Wistar-albino rats (280–310 g) | 1 ml/kg, 2 ml/kg and 3 ml/kg | 30 days | No microscopic or macroscopic adverse effects in the contralateral pleura and other tissues. No systemic effects. | 1 ml/kg did not cause adhesion, 2 ml/kg was effective but 3 ml/kg was deemed more appropriate. |
Yalcinkaya et al. 2019 [25] | Wistar-albino rats (250–300 g) | 3 ml/kg | 7 and 21 days | At least 1 rat died before the end of the study in each group. | NSAIDs seemed to reduce the formation of pleurodesis when used after the intervention. | |
Yildizhan et al. 2016 [26] | Wistar-albino rats (260–320 g) | 2 ml/kg | 30 days | No inflammation or adhesion in the contralateral pleura, liver or diaphragm. No sign of alveolar injury. | A group which received a 50:50 mix of ozone and 1 ml/kg autologous blood demonstrated better results compared to autologous blood alone (2 ml/kg). | |
Mitchem et al. 1999 [20] | New Zealand rabbits (4 kg) | 1 ml/kg | 30 days | No adverse effects. | No efficacy in contrast to Talc and doxycycline which had significant efficacy. |