Association between Caffeine Citrate and Incidence of Acute Kidney Injury in Preterms

Background: As a result of prematurity, Acute kidney injury (AKI) occurs commonly in preterm neonates and is associated with increased morbidity and mortality. (AKI) is defined as a rapid, potentially reversible deterioration in renal functions sufficient to result in accumulation of nitrogenous wastes in the body. Aim of the Study: the aim of this study was to determine whether preterm neonates who took caffeine citrate from the first day after birth were less likely to AKI within the first 7 days. Patients and Methods: This case control study was conducted on 100 preterm neonates at Neonatal Intensive Care Units (NICUS), Pediatric Department, Tanta University with gestational age less than (30 weeks) were grouped into group A and B. Group A 50 preterm neonates who received caffeine citrate from the first day after birth with dose (20 mg/kg) loading dose, and (5 mg/kg/dose) every 24hrs of maintenance dose, given as slow intravenous infusion over twenty to thirty minutes for a week. Group B 50 preterm neonates who did not receive caffeine citrate. Inclusion Criteria: all preterms <30 weeks admitted within first 24 hours after birth presented by respiratory distress according to Downes score. Exclusion Criteria: newborns with congenital heart disease except non-significant PDA, neonatal mortality < 48 h of life, clinical signs suggest chromosomal anomalies, newborns with congenital renal anomalies. Hematological Investigations: serum albumin, serum creatinine, blood urea. Urinary Investigations: measuring urine output. Results: There was a statistically significant difference between the two studied groups as regard serum creatinine in day (5,7) (p<0.001), urea in day 7 (p value <0.001), serum albumin in day (5,7) (p value ≤ 0.05), urine output in day (4,5,6,7) (p value ≤0.05), AKI incidence (p value <0.001). Conclusion: Caffeine Citrate administration in preterm neonates from the first day of life for one week was associated with reduced occurrence and severity of AKI.

Effect of very early use of caffeine citrate in preterm neonates needing respiratory support

Background Caffeine citrate is one of the most widely used medications in neonatal intensive care units. It is a respiratory stimulant which has well established therapeutic effects in apnea and extubation. Little is known about the very early use of caffeine citrate in preterm neonates. We aim to explore the effectiveness of its very early use in reducing the duration of the respiratory support used and not just extubation. Objectives to study the effect of the very early use of caffeine citrate in preterm neonates on morbidity and short-term neonatal outcomes. Subjects and Methods A prospective phase 3 clinical trial was carried out on 54 preterm neonates less than 34 weeks of gestation who require respiratory support and were given caffeine citrate in two different settings, over a period of one year. Patients were randomly allocated to one of two groups, the first group was given caffeine citrate at initiation of respiratory support(CPAP, NIPPV and IPPV). The second group received caffeine citrate 6 hours before weaning of the respiratory support used. Caffeine citrate was stopped after complete removal of the respiratory support used. Both groups were compared as regard the duration of each respiratory support used separately and the total duration of respiratory support needed for each patient. Results The duration of IPPV used in patients was significantly lower in the patients that received early caffeine citrate. Total duration of the respiratory support needed for each patient was significantly lower in the early group. There was no significant difference in the development of complications related to the drug use between both groups. The total duration of NICU stay was significantly lower in the early group than the other group. Conclusion The Early initiation of caffeine citrate has effectively and safely decreased duration of respiratory support used and NICU stay without the development of any complications. Key words early caffeine citrate, preterm neonates, respiratory support. *CPAP: Continuous positive airway pressure NIPPV: Non invasive positive pressure ventilation IPPV: Intermittent positive pressure ventilation NICU: Neonatal Intensive care unit

The risk of development of acute kidney injury in full-term infants with administration of methylxanthines

Exploring new possibilities for the use of methylxanthines to prevent the development of acute kidney injury (AKI) in full-term infants with perinatal asphyxia. Aim: to evaluate the efficacy and safety of methylxanthines in full-term infants for the prevention and conservative treatment of acute kidney injury. Materials and methods. To test the effectiveness of the proposed method of AKI treatment, 38 infants were chosen and divided into 2 groups by random selection. Nursing and intensive care were according to current legislation (Order of the Ministry of Health of Ukraine No. 225 of March 28, 2014). The main group (n = 20) received therapy with caffeine citrate, the comparison group (n = 18) – theophylline. Both of these drugs were used to prevent the development of acute kidney injury – stage II and III according to KDIGO. Results. A significant difference in serum creatinine was found in the main group - the level of serum creatinine was higher than in the comparison group, but did not exceed the physiological norm. GFR on the 3rd day of life was higher with administration of theophylline, but in the group of caffeine did not exceed the reference values of the norm. No differences between urea levels and diuresis rates were found in the groups. The initial results indicate the lack of statistical significance when using various drugs of the methylxanthine group, namely theophylline and caffeine citrate. This is explained by the fact that in the main group 65.00 % (n = 13) of patients had AKI stage 0 according to KDIGO, and 35.00 % (n = 7) had stage I. In the comparison group, 55.56 % (n = 10) and 44.44 % (n = 8), respectively. Stages II and III in both groups of the study did not develop, the obtained data are equivalent – U = 163,00; P = 0,6296. However, the use of caffeine citrate may become a priority due to a better safety profile compared to theophylline. Caffeine is less likely to cause adverse effects in the form of non-pathological bile vomiting and has significantly lower relative risk of non-pathological bile vomiting in infants (RR 0.26 (95 % CI 0.10; 0.66)). Conclusions. Conservative methylxanthine therapy in full-term infants with perinatal asphyxia prevents the development of stages II and III of AKI according to KDIGO. However, it is necessary to continue the collection of material to increase the statistical significance, as well as to study the early and long-term consequences of this therapy.

Evaluation of the Use of Caffeine Citrate Maintenance Doses >5 mg/kg/day in Preterm Neonates for Apnea of Prematurity

OBJECTIVE Caffeine citrate doses &gt;5 mg/kg/day are frequently used for apnea of prematurity. The primary objective was identification of patients maintained on 5 mg/kg/day (Group 1). Secondary objectives included identification of patients requiring dose increases: 7.5 mg/kg every 24 hours (Group 2), 10 mg/kg every 24 hours (Group 3), and 5 mg/kg every 12 hours (Group 4); comparison of demographics and clinical characteristics; and identification of patients requiring dose adjustments owing to caffeine-associated tachycardia. METHODS Retrospective study of neonates born between 23 to &lt;31 weeks' gestation, receiving caffeine between January 1, 2015, and July 31, 2019. Patients receiving caffeine &lt;1 week, initial maintenance dose &gt;5 mg/kg/day, or with congenital abnormalities were excluded. Descriptive and inferential statistics were performed, with a p &lt; 0.05. RESULTS Overall, 281 patients were included, with 99 (35.2%) in Group 1; 56 (19.9%) in Group 2; 47 (16.7%) in Group 3; and 79 (28.1%) in Group 4. Significant differences in gestational age were noted, with Group 3 and 4 patients being more premature than Groups 1 and 2 (p &lt; 0.001). Dose increases occurred at a median postnatal age and postmenstrual age of 13.0 days and 31.4 weeks in Group 2; 17.0 days and 30.3 weeks in Group 3; and 16.0 days and 30.1 weeks in Group 4. Significant differences were noted for development of tachycardia requiring dose adjustment, with Groups 3 and 4 having the highest percentage (p &lt; 0.001). CONCLUSIONS Two-thirds received caffeine citrate doses &gt;5 mg/kg/day, with 44% receiving 10 mg/kg/day. Further exploration is necessary to determine the optimal PNA or PMA for dose adjustments.

Hidden risks of respiratory support in neonates: retinopathy of prematurity

Background. Retinopathy of prematurity (RP) is the main reason for visual disability in premature survivors. RP increases chances for re-hospitalization and re-admission for special help by 1.5–4 times. It can lead to blindness in childhood. Risk factors for RP are mechanical ventilation and oxygen as well as weight gain problems in the postnatal period. The purpose was to assess the influence of different elements of intensive care on the development of severe RP, particularly, respiratory support strategies. Materials and methods. Simple retro-prospective blind non-randomized trial in two separate medical centers of Dnipro enrolled 122 premature neonates with the gestational age of 28–32 weeks from 2016 till 2020. The endpoint for assessment was the development of moderate and severe RP. We performed a univariate logistic regression analysis to analyze the odds ratio and 95% confidence interval (95% CI) for main risk factors. The confidence p level was 0.05. Results. Eighteen percent of premature neonates presented with moderate or severe RP on the 14th day of intensive care according to routine ophthalmologic examination. The moderate and severe RP was associated with an increase in length of noninvasive respiratory care by 4 times (p = 0.01), prolonged conventional ventilation by two-fold (p = 0.33), CPAP length by 4.5 times (p = 0.05), longer usage of additional oxygen (FiO2 > 30 %) by 4 times (p = 0.01). AUC for all these predictors ranged from 0.63 to 0.68. We found the following main predictors of retinopathy. According to statistics, every single day of respiratory support increases the chance of moderate or severe RP by 7–9 % depending on ventilation method, and caffeine citrate usage increases this chance by 6 times. Every 100 g of weight decrease is associated with a 16% increase in RP development risk (p = 0.03). Conclusions. Any respiratory support increases the risk of moderate and severe RP. Thus, the usage of these intensive care modalities can’t be preventive. Attentive modes of weight control should help in the prophylaxis of RP development as well as usual ophthalmologic examinations.

Early High-dose Caffeine Improves Respiratory Outcomes in Preterm Infants

The objective of the study is to determine if early high-dose caffeine (HD) therapy is associated with shorter duration of mechanical ventilation, bronchopulmonary dysplasia (BPD), or decreased need for mechanical ventilation. We conducted a single center, retrospective cohort study of 273 infants less than 32 weeks gestational age (GA). Infants receiving early HD (10 mg/kg/day maintenance) caffeine citrate started within 24 h of life were compared with those receiving LD (6 mg/kg/day) with variable timing of initiation using linear and logistic regression models. The infants in the early HD group had 91.4 (95% confidence interval (CI): −166.6, −16.1; p = 0.018) less hours of mechanical ventilation up to 36 weeks PMA or discharge as compared with the LD group. Moreover, infants in the HD group had 0.37 (95% CI: 0.14, 0.97; p = 0.042) times lower odds of developing moderate/severe BPD compared with the LD group. Infants receiving early HD caffeine had improved respiratory outcomes with no increase in measured comorbidities. Large prospective studies are needed to determine the long-term outcomes of using high-dose caffeine prophylaxis for preterm infants.