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Table 4 Detailed evaluation of previous experimental animal studies (rats and rabbits) of pleurodesis

From: Comparison of Hydroxyethyl starch 130/0.4 (6%) with commonly used agents in an experimental Pleurodesis model

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.