Potential of high dose caffeine citrate to cause intracranial hemorrhage in a premature rat model

Abstract

Aim: To determine whether caffeine citrate, used in the treatment of apnea of ​​prematurity, poses a risk of intracranial hemorrhage (ICH) when used at high doses (100 mg/kg) in premature neonates.

Methods: Wistar albino rats are divided into 3 groups. Each group consists of 8 rats. The first group constituted the control group and was not given any medication. The second group was determined as the group given normal dose (20 mg/kg) caffeine citrate, and the third group was determined as the group given high dose (100 mg/kg) caffeine citrate. Brain tomography was performed on the baby rats immediately after birth to rule out congenital ICH. 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 orogastric tube. At the end of the 2nd hour after the first brain tomography, all rats in the 3 groups were subjected to a control brain tomography, and xylazine (1mg/kg) and high dose ketamine (20 mg/kg) were administered intraabdominally and sacrificed. The rats were sacrificed due to intracranial hemorrhage that was too small to be detected on brain tomography imaging, and then their brain tissue was evaluated histopathologically. Bleeding at the microscopic level was investigated by staining with hematoxylin-eosin dye.

Results: There was no intracranial hemorrhage detected in both brain tomography and brain tissue pathology of all the baby rats which was determined as the control group, normal dose (20 mg/kg), and high dose (100 mg/kg) caffeine citrate group.

Conclusions: It was determined that caffeine citrate, used in the treatment of apnea of prematurity, did not cause intracranial bleeding in premature rats at high doses (100 mg/kg) in an experimental setting. It provides clues about whether high doses of caffeine will cause intracranial hemorrhage in humans.