Stryzhak L. Optimization of intensive care for acute kidney injury in full-term newborns with moderate and severe hypoxic-ischemic encephalopathy

The aim of the work is to improve the results of intensive care of full-term newborns with moderate or severe hypoxic-ischemic encephalopathy by improving the diagnosis and conservative therapy of acute kidney injury. The study analyzed patients' anamnestic data and identified all perinatal events contributing to the development of hypoxic-ischemic encephalopathy (HIE) as an inherent risk of developing acute kidney injury (AKI). On the basis of clinical, laboratory and instrumental methods of examination, the function of kidneys in infants was evaluated and the effectiveness of the preventive use of methylxanthines was proven. 50 (100%) newborns with a gestational age of 37-42 weeks were included in the prospective randomized controlled trial. All patients were treated in the neonatal intensive care unit of the Zaporizhzhia Regional Clinical Children's Hospital for moderate or severe HIE and required a program of systemic therapeutic hypothermia. Taking into account the high risk of developing acute renal injure in the study patients, methylxanthines were prescribed for the purpose of nephroprotection. Patients were randomized into 2 groups using the method of random selection. The first group consisted of 25 infants who received theophylline at a dose of 3 mg/kg intravenously at 6-hour intervals during the first 3 days of life (recommendation of KDIGO 2012, but without announcing the dosage regimen of the drug). The second group consisted of 25 representative patients who were prescribed caffeine citrate at a dose of 10 mg/kg intravenous drip with an interval of 12 hours on the first day of life, 5 mg/kg with an interval of 12 hours on the 2nd and 3rd day. Administration of the first dose of methylxanthines in both groups was carried out no later than 6 hours after birth. A comprehensive assessment of neurological and somatic statuses and determination of the degree of severity of AKI according to the modified neonatal criteria of the KDIGO scale (2012) was carried out on the 1st, 3rd and 5th day after birth, using clinical, biochemical, ultrasound research methods, continuous NIRS and aEEG monitoring. The general condition of newborns was assessed according to the criteria of the Apgar scale. For 1 minute of life, 4.00 (3.00; 6.00) points were obtained, 68.75% needed resuscitation. At the end of 5 minutes - 6.00 (5.00, 7.00) points, 36.00% of patients had ≤ 5 points, at the 10th minute 10.00% of newborns had an Apgar score of ≤ 5 points. The degree of damage to the central nervous system was determined according to the Thompson scale (1997), according to which a moderate stage of HIE was diagnosed in 72.00% of patients, the average score was 13.00 (12.00; 13.50) points, in 28.00% - severe HIE and 17.00 (16.00; 18.00) points. The distribution of children according to the degree of HIE was carried out equally. For the first time, administration of caffeine citrate was used in full-term newborns receiving total therapeutic hypothermia for the prevention and treatment of acute kidneydamage, which develops against the background of hypoxic conditions accompanying the perinatal period, which is the latest in the practice of neonatal intensive care. On the basis of the obtained data, the approach to the choice of the method of diagnosis and treatment of full-term newborns with renal disorders of various degrees of severity against the background of moderate or severe HIE was substantiated and improved. The significance of the use of early biochemical and instrumental markers for the diagnosis of acute kidney injury which allows preventing irreversible stages of damage to the renal parenchyma is substantiated. The study proved that the use of this strategy of intensive therapy prevents the development of the III stage of AKI KDIGO (2012) and shortens the length of stay of patients in intensive care beds. Prophylactic administration of methylxanthines in the first 6 postnatal hours during the entire cooling period and until the end of the rewarming phase is recommended in fullterm newborns with a moderate and severe stage of hypoxic-ischemic encephalopathy who meet the criteria for involvement in therapeutic hypothermia. The scheme of methylxanthine therapy and their dosage regime, which helps to reduce the risk of developing acute kidney damage, has been developed and implemented in practical medicine. The efficacy and better safety profile of caffeine citrate for nephroprotection compared to theophylline, taking into account the adverse effects, is substantiated. A method of early diagnosis of hypoperfusion and optimization of hemodynamic disturbances to prevent the development of kidney dysfunction using spectroscopy of noninvasive permanent NIRS monitoring of tissue oxygen saturation is proposed. The importance of influence primarily on changes in indicators of cerebral rather than renal oxygenation in the management of hemodynamics has been proven.