Prophylactic Effect of Venous Caffeine on Apnea in the Very Preterm Infants

Due to the importance of prevention of apnea of prematurity in the very preterm infants and the side effects of using methylxanthines in preterm infants, the present study was conducted and aimed at investigating the effects of prophylactic caffeine on the incident of apnea (short-term consequence). This is a clinical–experimental trial, in which the infants were included after receiving written consent from their parents. The infants were randomly divided into two groups, namely, Group A (receive caffeine) and Group B (did not receive caffeine). After sampling of the collected data, the two groups were analyzed using statistical tests using SPSS software 23. Among the 50 infants in the caffeine group and 50 infants in the control group, 1 (2%) and 2 (4%) infants required long-term oxygen, respectively. Three (6%) infants from the caffeine group and 2 (4%) infants from the control group had an intraventricular hemorrhage. Two (4%) infants from the caffeine group and 1 (2%) infant from the control group had a positive patent ductus arteriosus and needed treatment. Among the 50 infants in the caffeine group and 50 infants in the control group, 7 (14%) and 9 (18%) infants had apnea, respectively. According to the Fisher's exact test, there was no significant difference between the incident of apnea in the two groups (P = 0.58). Ten (20%) infants from the caffeine group and 7 (14%) infants from the control group died. The prescription of prophylactic caffeine had no effect on the incident of apnea in the infants. Hence, the use of that should be limited to the preterm infants lower than 1250 g in the prophylactic form.

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial

The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats.

The purpose of this study is to investigate the effects of combined carbohydrate (CH) and caffeine (CAF) supplementation on the sports performance of basketball players. A randomized crossover controlled experimental design was employed. A total of 32 collegiate-level basketball players were randomly assigned to one of the four groups: placebo (PLA), CH (30 g/h glucose solution) group, CAF (3 mg/kg body mass) group, and CH + CAF (combined intervention) group. Participants underwent a series of tests, including the countermovement jump (CMJ), 20-m sprint (20 m), change-of-direction and acceleration test (CODAT), Yo-Yo intermittent recovery test level 1 (Yo-Yo), free throw (FT) test, and straight-line dribbling speed (SLDS) test. Heart rate (HR) and blood lactic acid (BLA) levels were also monitored during the tests. The results revealed that, in the CMJ, 20 m, and CODAT tests, the CAF and CH + CAF groups outperformed the PLA group significantly (p < .05). In the Yo-Yo test, both the CH and CH + CAF groups demonstrated significantly better performance compared with the PLA group (p < .01). However, no significant differences were observed among the groups in the FT and SLDS tests (p > .05). Notably, the BLA levels in the CAF group were significantly higher than those in the PLA and CH groups 1-min postexercise (p < .05), and also significantly higher than in the CH + CAF group (p < .01). Three min after exercise, BLA levels in both the CH + CAF and PLA groups increased significantly (p < .05), with the CH + CAF group showing a greater increase compared with the CH group (p < .01). During exercise, the HR in the CH group was significantly lower than in the PLA group (p < .01), while the HR in the CAF group was significantly higher than in the PLA group (p < .01). Furthermore, the HR in the CH group was significantly lower compared with the CAF group (p < .01), and the HR in the CH + CAF group was significantly higher than in the CAF group (p < .01). After exercise, the HR in the CH group remained significantly lower than in the CAF group (p < .01). In conclusion, the combined supplementation of CH + CAF can effectively improve the overall sports performance of basketball players, with a certain recovery effect on physiological responses, but has no significant impact on professional skills. Overall, joint supplementation has not shown significant synergistic effects, but it can still be used as one of the nutritional strategies, with flexible selection of usage based on actual needs.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia, which may be severe enough to require resuscitation including use of positive pressure ventilation. Two forms of methylxanthine (caffeine and theophylline) have been used to stimulate breathing in order to prevent apnea and its consequences. To evaluate the effect of caffeine compared with theophylline treatment on the risk of apnea and use of mechanical ventilation in preterm infants with recurrent apnea. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases in August 2009: Oxford Database of Perinatal Trials; Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2009); MEDLINE (1966 to April 2009); and EMBASE Drugs and Pharmacology (1990 to April 2009), previous reviews including cross references. Randomized and quasi-randomized trials comparing caffeine to theophylline for treating apnea in preterm infants and reporting effects on apnea event rates. Each author assessed eligibility and trial quality, extracted data separately and compared and resolved differences. Study authors were contacted for additional information. Five trials involving a total of 108 infants were included. The quality of most of these small trials was fair to good. No difference in treatment failure rate (less than 50% reduction in apnea/bradycardia) was found between caffeine and theophylline after one to three days treatment (based on two studies) or five to seven days treatment (based on one study). There was no difference in mean apnea rate between caffeine and theophylline groups after one to three days treatment (based on five trials) and five to seven days treatment (based on four trials).Adverse effects, indicated by tachycardia or feed intolerance leading to change in dosing, were lower in the caffeine group (summary relative risk 0.17, 95% CI 0.04 to 0.72). This was reported and consistent in three studies.No trial reported the use of ventilation and no data were available to assess effects on growth and development. Caffeine appears to have similar short-term effects on apnea/bradycardia as does theophylline although caffeine has certain therapeutic advantages over theophylline. Theophylline is associated with higher rates of toxicity. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials.

Objective: Our first aim was to investigate the effects of caffeine on preterm infants' respiratory functions and brain cortical activity (conventional and amplitude-integrated electroencephalography (cEEG and aEEG)). Secondary aim was to study its long-term effects on respiratory system and electroencephalographic maturation by 36 weeks post-menstrual age. Methods: Prospective observational study on 33 consecutively admitted preterm infants less than 34-weeks-gestation. cEEG and aEEG, cardiopulmonary and sleep state were recorded in 20 preterm infants, before, during and 2-hours after intravenous (IV) caffeine (caffeine Group), and for 13 preterms (control group). Both groups were subjected to assessment of cerebral cortical maturation by cEEG and aEEG at 36-weeks post-menstrual age as an outcome measure. Results: IV caffeine administration significantly increased heart rate (p = 0.000), mean arterial blood pressure (p = 0.000), capillary oxygen saturation (p = 0.003), arousability (p = 0.000) and aEEG continuity (p = 0.002) after half an hour. No clinical seizures were recorded and non-significant difference was found in electrographic seizures activity in cEEG. At 36-weeks post-conceptional age, NICU stay was significantly longer in controls (p = 0.022). aEEG score was significantly higher in caffeine group than the control group, (p = 0.000). Conclusions: Caffeine increases preterm infants’ cerebral cortical activity during infusion and results in cerebral cortical maturation at 36weeks, without increase in seizure activity.

Objective To study the clinical efficacy of caffeine in premature infants receiving mechanical ventilation and related complications. Method From January 2014 to September 2016, preterm infants (28w≤GA<33w) treated with nasal continuous positive airway pressure (NCPAP) or conventional mechanical ventilation (CMV) in neonatal intensive care unit were studied. They were randomly assigned into the caffeine group and the control group. The caffeine group received caffeine when NCPAP ventilation was applied or adjusting to synchronized intermittent mandatory ventilation (SIMV) mode. The control group was injected with 5% glucose without caffeine.The t test and χ2 test were used to analyze the clinical efficacy and related complications. Result A total of 96 patients receiving NCPAP ventilation were collected (birth weight between 1 300~2 100 g), including 51 cases in caffeine group and 45 cases in the control group. 84 cases received CMV ventilation (birth weight between 1 000~1 499 g), with 43 cases in the caffeine group and 41 cases the control group. Among the NCPAP infants, the incidence of failure to withdraw ventilator (0% vs. 13.3%) and the incidence of bronchopulmonary dysplasia (3.9% vs. 17.8%) were lower in the caffeine group than the control group. The duration of assisted ventilation and hospital stay in the caffeine group were shorter than the control group [(6.2±3.1) d vs. (8.2±3.2) d, (16.3±8.7) d vs.(19.5±9.2) d], the differences were statistically significant (P 0.05). Conclusion Caffeine can help reduce the incidences of withdrawal failure, bronchopulmonary dysplasia, ventilation duration and hospital stay when using NCPAP and CMV ventilation. Key words: Caffeine; Continuous positive airway pressure; Ventilators, mechanical; Bronchopulmonary dysplasia; Infant, premature

This study investigates whether daily supplementation of 120-150 mg of caffeine can relieve symptoms of Burning Mouth Syndrome (BMS) compared to alpha-lipoic acid (ALA) and a control group. In this randomised controlled trial, 118 BMS patients were divided into three groups: caffeine, ALA, and control. The caffeine group received 120-150 mg of caffeine daily, the ALA group received 200 mg of ALA three times daily, and the control group received no interventions. Symptom relief was assessed over 2 weeks using the Visual Analog Scale (VAS), with subgroup analyses based on symptom subtypes, disease duration, symptom sites, and characteristics. The VAS of BMS patients in the caffeine and ALA groups exhibited significant reductions (p < 0.0005). The caffeine group exhibited a 65.1% symptom relief rate compared to 46.5% in the ALA group and 12.5% in the control group. Significant differences in symptom relief were noted between the caffeine and control groups (p < 0.0005) and between the ALA and control groups (p = 0.0032). No significant difference was observed between the caffeine and ALA groups (p = 0.084). Type I BMS patients in the caffeine group showed greater symptom relief than those in the ALA group (p = 0.026). Both caffeine and ALA effectively treated BMS, with caffeine showing higher efficacy in Type I patients. Treatments were well-tolerated with minimal adverse effects, suggesting caffeine and ALA as promising treatments for BMS, warranting further research on their long-term effects and mechanisms of action. [The study was registered on ClinicalTrials.gov (Identification No. NCT06195137).].

Although caffeine has been shown to improve important clinical outcomes, in the few studies that compared caffeine to other methylxanthines, there might be little to no difference in mortality, bronchopulmonary dysplasia, and duration of hospital stay. The evidence is very uncertain about the effect of caffeine compared to other methylxanthines on long-term development and side effects. Although caffeine or other methylxanthines are widely used in preterm infants, there is little direct evidence to support the choice of which methylxanthine to use. More research is needed, especially on extremely preterm infants born before 28 weeks of gestation. Data from four ongoing studies might provide more evidence on the effects of caffeine or other methylxanthines.

Caffeine Administration to Prevent Apnea in Very Premature Infants

Early application of caffeine improves white matter development in very preterm infants

The purpose of this study was to evaluate the effects of dietary caffeine during gestation and lactation on the acid solubility of molar teeth of weanling rats. Nineteen pregnant dams were divided into two groups. The 9 dams in the control group were fed a 20% protein diet supplemented with caffeine (2 mg/100 g BW) throughout the experiment. At birth, 8 pups were randomly assigned to each dam. Pups were killed on day 22. The 1st and 2nd molars were removed from each pup's maxilla and mandible. Four randomly selected molars from each litter were placed in a chamber and bathed with a flow of acid solution and the amount of mineral dissolved from the enamel was determined. The results showed that the amount of dissolved Ca and Mg from enamel surfaces of 1st molars from rats in the caffeine group after exposure to acid was consistently greater than that of the non caffeine group. In the 2nd molars there was no significant difference between caffeine and noncaffeine groups. Scanning electron microscopy revealed an alteration of the enamel surface of the 1st molars of the caffeine group after acid exposure. These results indicate that caffeine intake during gestation and lactation would have a deleterious effect on dental enamel of 1st molars in newborn rats.

After completing this article, readers should be able to: 1. Describe the epidemiology and pathophysiology of gastroesophageal reflux (GER) in preterm neonates. 2. Delineate the associations of GER with apnea, chronic lung disease, behavior, and growth of preterm infants. 3. Review the investigations used to evaluate GER in preterm infants. 4. Describe nonpharmacologic and pharmacologic therapies for GER. Gastroesophageal reflux (GER) is a normal physiologic event occurring across the age spectrum. It may contribute to a variety of disorders, including esophagitis, feeding problems, and airway disease in all age groups. (1) A large number of symptoms and signs have been purported to be caused by GER despite a lack of data showing a clear association between a specific symptom and GER. In preterm infants, empiric therapy often is administered using agents of unproven efficacy and safety to treat symptoms that likely are unrelated to GER. In a survey on management practices for GER in preterm infants, common treatment strategies included positioning (98%) and slopes (96%), histamine 2 (H 2) receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetics (79%), proton pump inhibitors (PPIs) (65%), and dopamine receptor antagonists (53%). (2)(3) The safety, efficacy, and appropriate dosing recommendations for most medical therapies remain uncertain in neonates. In this review, we attempt to summarize the current literature regarding physiology, pathophysiology, and diagnostic and management strategies for GER pertinent to the neonate, with an emphasis on the preterm infant. GER describes the retrograde movement of stomach contents (air or feeding, liquid or semisolid, acid or alkaline, enzymes or bile salts) into the esophagus. GER disease (GERD) occurs when GER causes symptoms or signs such as pain, poor weight gain, esophagitis, hematemesis, and airway symptoms, including apnea, aspiration, recurrent pneumonia, chronic lung disease (CLD), or large airway inflammation. However, any of these symptoms or signs …

After completing this article, readers should be able to: 1. Delineate the rationale for inhaled nitric oxide (iNO) use in respiratory distress syndrome. 2. List the toxicities of iNO. 3. Describe the primary findings of iNO therapy in major clinical trials. Respiratory distress syndrome (RDS) has been a major factor determining the limits of viability in the preterm infant. RDS is, in large part, the result of surfactant deficiency. Surfactant replacement and antenatal steroid use are the two major advances in the treatment of RDS to date and have resulted in significant decreases in mortality and chronic lung disease (CLD). Surfactant replacement became widely available in 1991, and antenatal steroids achieved widespread use following the National Institutes of Health Consensus Conference in 1994. (1) However, substantial mortality and CLD still are seen in the very low-birthweight infant (Fig. 1). Figure 1 National Institute of Child and Human Development (NICHD) Neonatal Research Network mortality and CLD rates for 2003 in preterm infants born at 23 to 30 weeks’ gestation. Following the identification of nitric oxide (NO) as the vascular endothelial relaxing factor, use of the agent has moved rapidly from bench to bedside. Inhaled nitric oxide (iNO) was found to improve oxygenation in adult and pediatric patients who had hypoxic respiratory failure. (2)(3)(4) Subsequent randomized, controlled trials in term and near-term infants who had hypoxic respiratory failure demonstrated an improvement in oxygenation as well as a significant decrease in death or the need for extracorporeal membrane oxygenation. (5)(6)(7) Following United States Food and Drug Administration review of these trials, iNO was approved for use in term and near-term infants who had hypoxic respiratory failure. The role of iNO in the preterm infant who has RDS has been an active area of investigation over the last decade. This …

Introduction: We performed this study to compare the effect of Caffeine and stretching exercise on Post Dural Puncture Headache (PDHP). Methods: In this Randomized Clinical Trial, 160 candidates for elective inguinal hernia surgery or varicocele surgery in Shahid Modares Hospital in Tehran, were assigned into the following groups using a computer-generated randomization table: caffeine group received Caffeine tablet (200 mg TDS); exercise group received stretching exercise; caffeine combine exercise group received Caffeine tablet (200 mg TDS ), and stretching exercise and control group received placebo tablets. After the end of the surgery, up to 48 h, the Visual analog scale (VAS) was recorded every 6hours by the same clinician. Results: The occurrence of PDPH was less in the caffeine and exercise combined group than in the control group. Also, the headache was more severe in the control group than in the caffeine group. Furthermore, the need for rescue analgesics was more in the control group than in the caffeine group. Conclusion: caffeine and exercise combined had better outcomes than placebo regarding PDHP.