Bronchopulmonary dysplasia (BPD) is one of the few diseases affecting premature infants that have continued to evolve since its first description about half a century ago. The current form of BPD, a more benign and protracted respiratory failure in extremely preterm infants, is in contrast to the original presentation of severe respiratory failure with high mortality in larger premature infants. This new BPD is end result of complex interplay of various antenatal and postnatal factors causing lung injury and subsequent abnormal repair leading to altered alveolar and vascular development. The change in clinical and pathologic picture of BPD over time has resulted in new challenges in developing strategies for its prevention and management. While some of these strategies like Vitamin A supplementation, caffeine and volume targeted ventilation have stood the test of time, others like postnatal steroids are being reexamined with great interest in last few years. It is quite clear that BPD is unlikely to be eliminated unless some miraculous strategy cures prematurity. The future of BPD prevention will probably be a combination of antenatal and postnatal strategies acting on multiple pathways to minimize lung injury and abnormal repair as well as promote normal alveolar and vascular development.
Adrenal Cortex Hormones ; therapeutic use ; Animals ; Bronchopulmonary Dysplasia ; prevention & control ; Caffeine ; therapeutic use ; Humans ; Oxygen ; therapeutic use ; Pulmonary Surfactants ; therapeutic use ; Respiration, Artificial

OBJECTIVETo investigate the current status of studies on drug therapy for apnea of prematurity (AOP) in the past decade in China and abroad, and to describe the research trends in the field.

METHODSCNKI and MEDLINE were searched with the key words "apnea of prematurity" and "treatment" for articles published in the past decade (January 2006 to December 2015). The articles were screened and the key words were extracted to establish the co-occurrence matrix. Ucinet 6.2 was used to plot the knowledge map.

RESULTSA total of 26 Chinese key words and 20 English key words were included. Those in the center of the co-existent knowledge map of Chinses keywords were "preterm infants", "apnea", "primary apnea", "naloxone" and "aminophylline"; while "apnea", "preterm infants" and "caffeine" located in the central place of the co-existent knowledge map of English keywords.

CONCLUSIONSMethylxanthines are still the major drugs for AOP; however, aminophylline is mainly used in China, while caffeine is mainly used in foreign countries. Other drugs such as naltrexone are also used in the clinical treatment of AOP.

Aminophylline ; therapeutic use ; Apnea ; drug therapy ; Caffeine ; therapeutic use ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVETo investigate the clinical efficacy and safety of caffeine citrate and aminophylline in the treatment of primary apnea in premature infants.

METHODSThe clinical data of 125 premature infants with primary apnea from March 2013 to March 2014 were retrospectively analyzed. According to the therapeutic strategy, the patients were divided into caffeine citrate group (n=65) and aminophylline group (n=60). The overall response rates and adverse reaction rates in the two groups were compared.

RESULTSThe overall response rate in the caffeine citrate group was 86% (56 cases), which was significantly higher than that in the aminophylline group (72%, 43 cases) (P<0.05). The adverse reactions in the caffeine citrate group included tachycardia (1 case), restlessness (5 cases), feeding intolerance (7 cases), electrolyte disturbance (2 cases), and high blood glucose (5 cases), the incidence of which was significantly lower than that in the aminophylline group (P<0.05).

CONCLUSIONSCaffeine citrate is more effective and causes fewer adverse reactions than aminophylline in the treatment of primary apnea in premature infants.

Aminophylline ; adverse effects ; therapeutic use ; Apnea ; drug therapy ; Caffeine ; adverse effects ; therapeutic use ; Citrates ; adverse effects ; therapeutic use ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Retrospective Studies

OBJECTIVETo determine the enhancement effects of caffeine on chemotherapy of transplanted osteosarcoma in Fischer 344/N rats.

METHODSOsteosarcoma-bearing Fischer 344/N rats were treated with cisplatin 2.5 mg/kg (Group DDP), caffeine 90 mg/kg x 2 d (Group caffeine), and cisplatin 2.5 mg/kg plus caffeine 90 mg/kg x 2 d (Group DDP+caffeine), and the control group was treated with normal saline in the same volume. All drugs were given by intra-peritoneum injection with micro-pump, in the rate of 0.5 ml/h. The tumor volume was measured and evaluated. The tumors were stained in TUNEL, and PCNA was detected with immunohistochemistry. The tumor growth inhibition rate, PCNA index and apoptosis index were calculated, and the survival time were recorded.

RESULTSThe tumor inhibition rate was -0.5219 +/-0.1429 in control group, 0.0362 +/-0.0957 in Group DDP, -0.4193 +/-0.1345 in Group caffeine, and 0.3646 +/-0.1313 in Group DDP+caffeine (P <0.01). PCNA index was 0.4587 +/-0.1312 in control group, 0.1847+/-0.0535 in Group DDP, 0.4381 +/-0.0706 in Group caffeine, and 0.0314 +/-0.0231 in Group DDP+caffeine (P <0.01). Apoptosis index was 0.0008 +/-0.0005 in control group, 0.0077 +/-0.0060 in Group DDP, 0.0011 +/-0.0003 in Group caffeine, and 0.0295 +/-0.0069 in Group DDP+caffeine (P <0.01). And the survival time was (33.63 +/-4.63)d in control group, (52.13 +/-11.74)d in Group DDP, (35.63 +/-5.15)d in Group caffeine, and (55.13 +/-16.23)d in Group DDP+caffeine (P <0.01).

CONCLUSIONCaffeine could enhance the anti-tumor effect of cisplatin in rat osteosarcoma.

Animals ; Antineoplastic Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; pathology ; Caffeine ; therapeutic use ; Cisplatin ; therapeutic use ; Drug Synergism ; Neoplasm Transplantation ; Osteosarcoma ; drug therapy ; pathology ; Rats ; Rats, Inbred F344

The knowledge on the pathogenetic mechanisms of bronchopulmonary dysplasia (BPD) has increased considerably over recent years. However, the incidence of the disease has not substantially been changed by our therapeutic approaches. This review summarizes the existing evidence for a number of respiratory and medical strategies to prevent or ameliorate the disease and gives recommendations for clinical practice. Oxygen plays an important pathogenetic and therapeutic role for BPD. Targeting infants at lower oxygen saturation levels than traditionally used seems to confer major advantages. There is no sufficient evidence for a routine use of respiratory strategies like permissive hypercapnia or inhaled nitric oxide to prevent BPD. Diuretics can ameliorate lung function transiently. High intramuscular doses of vitamin A can reduce the risk of BPD. Early or prophylactic surfactant might also be advantageous. Postnatal corticosteroids are effective but, due to their severe side effects, should be restricted to the severest cases. Alpha1-proteinase inhibitor and superoxide dismutase have no proven benefits for BPD. The role of erythromycin has not been completely elucidated yet. Innovative strategies like Clara Cell 10 kD protein still have to be assessed in future trials.
Antioxidants ; therapeutic use ; Bronchopulmonary Dysplasia ; prevention & control ; therapy ; Caffeine ; therapeutic use ; Diuretics ; therapeutic use ; Erythromycin ; therapeutic use ; Humans ; Incidence ; Infant, Newborn ; Nitric Oxide ; administration & dosage ; Oxygen ; therapeutic use ; Ureaplasma urealyticum ; drug effects

Apnea of prematurity (AOP) is one of the common diseases in preterm infants. The main cause of AOP is immature development of the respiratory control center. If AOP is not treated timely and effectively, it will lead to respiratory failure, hypoxic brain injury, and even death in severe cases. Caffeine is the first choice for the treatment of AOP, but its effectiveness varies in preterm infants. With the deepening of AOP research, more and more genetic factors have been confirmed to play important roles in the pathogenesis and treatment of AOP; in particular, the influence of single nucleotide polymorphism on the efficacy of caffeine has become a research hotspot in recent years. This article reviews the gene polymorphisms that affect the efficacy of caffeine, in order to provide a reference for individualized caffeine therapy. Citation.
Apnea/genetics* ; Caffeine/therapeutic use* ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases ; Polymorphism, Single Nucleotide

Caffeine,as an important component of refreshment beverage,has been used for a long history. In recent years,its effect on pain relief has been widely explored. As one of nonselective adenosine receptor blockers,caffeine plays different roles in the central and peripheral pain. This review explores the roles of caffeine in acute and chronic pain and the potential mechanisms.
Adenosine ; antagonists & inhibitors ; metabolism ; Caffeine ; pharmacology ; therapeutic use ; Central Nervous System Stimulants ; pharmacology ; therapeutic use ; Chronic Pain ; drug therapy ; Humans ; Pain ; drug therapy

OBJECTIVE: To study the clinical effect and safety of different maintenance doses of caffeine citrate in the treatment of apnea in very low birth weight preterm infants. METHODS: A total of 78 very low birth weight preterm infants with primary apnea were enrolled who were admitted from January 2016 to January 2018. They were randomly divided into high-dose caffeine group with 38 children and low-dose caffeine group with 40 children. Both groups received a loading dose of 20 mg/kg caffeine citrate, and 24 hours later, the children in the high-dose caffeine group were given a maintenance dose of 10 mg/kg, and those in the low-dose caffeine group were given a maintenance dose of 5 mg/kg. The two groups were compared in terms of response rate and incidence rate of adverse events. RESULTS: The high-dose caffeine group had a significantly higher response rate than the low-dose caffeine group (71% vs 48%; P<0.05). Compared with the low-dose caffeine group, the high-dose caffeine group had significantly shorter duration of apnea and time of caffeine treatment (P<0.05). There were no significant differences between the two groups in length of hospital stay and incidence rates of tachycardia, feeding intolerance, bronchopulmonary dysplasia, necrotizing enterocolitis, and intracranial hemorrhage (P>0.05). There was no significant difference in the mortality rate between the two groups (P>0.05). CONCLUSIONS Higher maintenance dose of caffeine citrate has a better clinical effect than lower maintenance dose of caffeine citrate in the treatment of apnea in very low birth weight preterm infants, without increasing the incidence rates of adverse drug reactions and serious complications in preterm infants.
Apnea ; drug therapy ; Caffeine ; therapeutic use ; Child ; Citrates ; therapeutic use ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies

OBJECTIVE: To compare the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants. METHODS: A total of 98 preterm infants with a gestational age of 28 - <34 weeks between April 2018 and December 2019 were enrolled. They were randomly administered with domestic (n=48) or imported caffeine citrate (n=50) within 6 hours after birth. The therapeutic effects, complications, adverse effects and clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in the incidence of apnea within 7 days after birth, daily frequency of apnea, the time of apnea disappearance, the failure rate of intubation-surfactant-extubation strategy, the time of non-invasive assisted ventilation, the duration of oxygen therapy, the duration of caffeine citrate therapy, the length of hospital stay, blood gas analysis results, liver and kidney function testing results between the two groups (P>0.05). There were no significant differences in the incidence of complications and the mortality rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse effects between the two groups (P>0.05). CONCLUSIONS The efficacy and safety of domestic caffeine citrate in the treatment of apnea are similar to those of imported caffeine citrate in preterm infants.
Apnea ; drug therapy ; Caffeine ; therapeutic use ; Citrates ; therapeutic use ; Double-Blind Method ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; Prospective Studies