To research if high dose caffeine citrate applied inmodels of the premature rat can cause intracranial bleeding

Aim: The aim of this study is to determine whether caffeine citrate, which is used for the treatment of apnea of prematurity, poses a risk of intracranial hemorrhage (ICC) if high dose (100 mg/kg) is used in premature newborns. The study was carried out with premature rat modeling. Methods and Results: This study was carried out in Tokat Gaziosmanpaşa University Hospital and Experimental Medicine Research Unit Center. It was made with Wistar Albino rats in 3 groups; 1st group consists of 8 rats, 2nd group 8, 3rd group consists of 8 rats. The first group constituted the control group and no medication was given. The second group was determined as the normal dose (20 mg/kg) caffeine citrate, and the third group was determined as the high dose (100 mg/kg) caffeine citrate group. Brain tomography was performed on the baby rats immediately after birth in order to exclude congenital intracranial hemorrhage. Normal dose (20 mg/kg) and high dose (100 mg/kg) caffeine citrate were given to the 2nd and 3rd groups, respectively, with the help of an orogastric tube. At the end of the 2nd hour after the first brain tomography, control brain tomography was taken and xylazine (1mg/kg) and high-dose ketamine (20mg/kg) were administered intraabdominal to each rat in 3 different groups and sacrificed. Since intracranial hemorrhage may be too small to be detected in brain tomography imaging, brain tissue pathology was also performed on the sacrificed rats. The sacrificed rats were delivered to the Medical Pathology unit for brain tissue pathology. Brain tissues are made into blocks by the specialist pathologist doctor working in the medical pathology unit; Bleeding at microscopic level was investigated by staining with hematoxylineosin dye. Brain tomography images were evaluated by a specialist radiologist in terms of intracranial bleeding. Intracranial hemorrhage was not detected in both brain tomography and brain tissue pathology of all baby rats in the control group, normal dose (20 mg/kg), high dose (100 mg/kg) caffeine citrate group, and 8 rats each. Conclusion: It was observed that Caffeine Citrate, which is used in the treatment of apnea of prematurity, did not cause intracranial bleeding at high doses (100 mg/kg) in premature rats in the experimental environment; It provides a clue as to whether it will cause intracranial hemorrhage in humans if given high doses. v More randomized controlled studies are needed to determine whether Caffeine Citrate for any reason will cause intracranial bleeding in high doses (100 mg/kg) Keywords: Caffeine citrate, Prematurity, Rat, Experimental, High Dose Supporting organization: BAP number 2021-50 dated 30. 05. 2021