Oxygen Therapy For Premature Infants Research Articles

Does recorded oximetry utilizing a consensus-based algorithm compare to polysomnography in discontinuing home oxygen therapy in premature infants?

Approximately a third of all extremely preterm infants diagnosed with bronchopulmonary dysplasia will require home oxygen therapy (HOT). Lack of consensus-based guidelines has led to significant variability in outpatient HOT management in the United States. A common assessment performed before discontinuing oxygen is a formal polysomnogram (PSG). PSGs are potentially undesirable due to cost, lack of convenient access, and parental stress, so alternative testing to determine the optimal timing of safe oxygen discontinuation are needed. We compared nocturnal recorded home oximetry (RHO) with PSG data in a cohort of patients from the RHO trial for patients who had recordings performed simultaneously to or within 24 h of their PSG. The RHO trial was a randomized, unblinded, multi-center trial comparing two oxygen management strategies. Parameters of oxygenation were compared between PSG and RHO, and nonoximegtry findings from the PSG that changed clinical management were identified. A total of 53 infants randomized to obtain a PSG as part of the RHO trial (55%) completed a PSG, and of those, 32 (64%) completed both a PSG with comparison RHO. There were more white infants in both groups than other races and ethnicities. Bland-Altman analysis showed a strong agreement of oxygen saturation time below 90% SpO2 between PSG and RHO results (slope = 1.014, p = 0.24). Results agreed in 96% of cases. RHO is a safe and effective alternative to PSG to assist in determination of discontinuing HOT in infants with BPD without other risks for sleep-disordered breathing.

Inhibition of FABP4 attenuates hyperoxia-induced lung injury and fibrosis via inhibiting TGF-β signaling in neonatal rats.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by interrupted alveologenesis and alveolar simplification caused by oxygen therapy in premature infants. Metabolic dysfunction is involved in the pathogenesis of BPD. Fatty acid-binding protein 4 (FABP4) is significantly increased in specific lung tissues in patients with BPD. Therefore, we investigated whether BMS309403, an FABP4 inhibitor that can mitigate tissue fibrosis, can regulate pulmonary fibrotic processes in newborn rats exposed to hyperoxia. Newborn rat pups were exposed to room air (RA; 21% O2 ) or 85% O2 from 5 to 14 days of age and were then allowed to recover in RA until 29 days of age. They received intraperitoneal injection with placebo (phosphate-buffered saline [PBS]) or BMS 309403 (0.5 mg or 1.0 mg kg-1 d-1 ) every other day from 4 to 14 days of age then were divided into O2 plus PBS or low dose or high dose and RA plus PBS or low dose or high dose groups. We assessed lung histology and evaluated lung collagen I, FABP4 as well as TGF-β1 expression at 14 and 29 days of age. In the hyperoxia injury-recovery model, prophylactic BMS309403 treatment reduced mean linear intercept values and FABP4 expression (p < 0.001). Prophylactic BMS309403 treatment mitigated pulmonary fibrosis and TGF-β1 expression immediately after hyperoxia exposure (p < 0.05). The attenuation of hyperoxia-induced alveolar developmental impairment and pulmonary fibrosis by FABP4 inhibition indicated that such inhibition has potential clinical and therapeutic applications.

The application of near-infrared spectroscopy in oxygen therapy for premature infants

Objective: This study used near-infrared spectroscopy (NIRS) to detect the pulmonary regional oxygen saturation (rSO2) of premature infants. The oxygenation state of the lung tissue was also evaluated, which provided preliminary evidence regarding the application of NIRS in oxygen therapy for premature infants.Methods: NIRS was used to measure the pulmonary rSO2 of 26 premature infants (gestational age <32 weeks). The correlations between pulmonary rSO2 and the arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), and pulse oxygen saturation (SpO2) were analyzed. The diagnostic value of NIRS was evaluated via both Pearson’s correlation and receiver operating characteristic (ROC) curve analyses.Results: Pulmonary rSO2 was positively correlated with both PO2 and SaO2; the linear correlation coefficients (r) were 0.544 (p = .004) and 0.515 (p = .007), respectively. No significant correlation was found between rSO2 and SpO2 (p = .098). SpO2 was positively correlated with PO2 (r = 0.402, p = .042) and SaO2 (r = 0.625, p = .001). NIRS could be used to predict hypoxemia (area under the curve [AUC] = 0.843; Youden’s index =0.654) when the pulmonary rSO2 was 62.39%, the sensitivity was 88.9%, and the specificity was 23.5% (p = .005) as well as predict hyperoxemia (AUC = 0.775; Youden’s index = 0.65) when the pulmonary rSO2 was 61.99%, the sensitivity was 100%, and the specificity was 35% (p = .045). SpO2 predicted hypoxemia (AUC = 0.784, p = .019) but not hyperoxemia (AUC = 0.7, p = .144).Conclusion: NIRS objectively reflects the changes in oxygenation in the lung tissue. This study provides evidence for the clinical application of NIRS.

Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia.

Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is maintained. Loss of pulmonary hypoxic vasoconstriction is not linked to alterations in oxygen-sensitive K(+) currents in pulmonary artery smooth muscle cells. Loss of hypoxic vasoconstriction is associated with early postnatal oxidative damage and corrected by an antioxidant diet. Perinatal hyperoxia damages carotid body chemoreceptor cell function and the antioxidant diet does not reverse it. The hypoxia-elicited increase in erythropoietin plasma levels is not affected by perinatal hyperoxia. The potential clinical significance of the findings in clinical situations such as pneumonia, chronic obstructive pulmonary disease or general anaesthesia is considered. Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55-60% O2 for the last 5-6days of pregnancy and 4weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2 -sensitivity of K(+) currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life.

Mechanism for p47phox-induced reactive oxygen species increasing after oxygen therapy in premature infants

Objective To explore the mechanism for the increase in reactive oxygen species regulated by p47phox of nicotinamide adenine dinucleotide phosphate(NADPH) oxidase subunit in peripheral blood mononuclear cells(PBMCs) after oxygen therapy in premature infants. Methods According to different volume fractions of oxygen, premature infants less than 32 weeks were divided into 3 groups: fractional concentration of inspired oxygen(FiO2) 40% as high concentration oxygen group.Premature infants less than 32 weeks without oxygen was control group.After 48 h, 3 mL blood was collected via radial artery from each group, PBMCs and serum were separated.Then intracellular reactive oxygen species (ROS) by confocal laser scanning microscopy, malondialdehyde(MDA) within serum by thiobarbituric acid colorimetric, and the location and activation rate of p47phox through immunofluorescence. Results After premature infants were exposed to oxygen, as the oxygen volume fraction was increasing, ROS and MDA gradually rised.More PBMCs with p47phox translocated to membrane, then the translocation rate of p47phox also increased.Compared with the control group, ROS were significantly higher(q=4.48, 6.5, 16.22, all P<0.05) among the other 3 groups; MDA significantly increased as well(q=5.08, 8.22, 12.76, all P<0.05); the activation rate of p47phox also had significant differences(χ2=134.008, P<0.05); compared with the middle concentration oxygen group, the high concentration oxygen group had higher ROS and MDA(q=15.03, 4.53, all P<0.05); the activation rate of p47phox increased significantly(χ2=19.26, P<0.05). Conclusions After oxygen exposure, p47phox translocated to membrane may regulate the NADPH oxidase-derived ROS increase in extremely premature infants. Key words: Infant, premature; Oxygen; Reactive oxygen species; malondialdehyde; p47phox

SUPPORTing Premature Infants

* Abbreviations: OHRP — : Office for Human Research Protections SUPPORT — : Surfactant Positive Pressure, and Oxygenation Randomized Trial The Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) tried to determine the safest dose of oxygen for premature infants. The federal Office for Human Research Protections (OHRP) determined that the consent process for the study violated federal regulations by failing to inform parents of “reasonably foreseeable risks” of death or blindness.1 The New York Times agreed, calling these failures “startling and deplorable.2 The New England Journal disagreed. They found the consent forms adequate and the accused the OHRP of “casting a pall over the conduct of clinical research.”3 Leaders of the NIH agreed.4 The difference of opinion turns, in part, on the ways that we define the relative risks of research, on the one hand, and, on the other hand, the risks of widely used but inadequately studied conventional therapies. Ten years ago, Cole et al5 summarized the state of knowledge about oxygen therapy for premature infants: “We do not understand optimal oxygenation management in extremely low gestational age neonates (<28 weeks’ gestation). No randomized controlled trial has clarified the relation between retinopathy of prematurity and blood oxygen, transcutaneous oxygen, or oxygen saturation levels.” As a result, they noted, “neonatal care providers differ widely, with no consensus in their policies, practices, and strong beliefs regarding oxygen management in both the early and later neonatal courses of premature infants.” They called for prospective randomized trials to address this crucial gap in knowledge because “continued treatment of millions of premature infants in ignorance of what is safe and effective oxygenation is not an option.” Today, the situation is different because such studies were designed and conducted in the United States,6 Canada, Australia, New Zealand, and the United Kingdom.7 In the United States, SUPPORT was a National Institutes of Health–sponsored, multicenter, prospective randomized trial of … Address correspondence to John D. Lantos, MD, Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108. E-mail: jlantos{at}cmh.edu

Bronchial responsiveness to methacholine and adenosine 5′-monophosphate in preschool children with bronchopulmonary dysplasia

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, but it is also frequently present in children and adults with chronic obstructive lung diseases. Bronchopulmonary dysplasia (BPD) is a chronic lung disease, most commonly developing after mechanical ventilation and oxygen therapy in premature infants. BHR is usually measured by bronchial challenges, using direct or indirect stimuli. The aim of this study was to evaluate BHR to direct and indirect stimuli in young children with BPD. Methacholine and adenosine 5'-monophosphate (AMP) bronchial challenges were performed on preschool children with BPD (n = 19), using a modified auscultation method. The endpoint was defined as the appearance of wheezing and/or oxygen desaturation. The results obtained were then compared with those of asthmatic (n = 25) and control (n = 23) preschool children. A positive response to methacholine (endpoint concentration, < or = 8 mg/ml) was observed in 89.5% (17/19) of patients with BPD, but a positive response to AMP (endpoint concentration, < or = 200 mg/ml) was observed only in 21.1% (4/19). All patients with asthma responded positively to methacholine, and most (23/25, 92.0%) of them also responded positively to AMP. The majority of controls were unresponsive to both challenges. BHR to methacholine is a frequent finding in preschool-age survivors of BPD, but is usually not accompanied by BHR to AMP. This suggests that most patients with BPD do not have the inflammatory airway response which is characteristic of asthmatic patients.

CONCLUSIONS

The problem of oxygen therapy for premature infants is far from being solved. There appears to be no concentration of oxygen in excess of that in air that is not associated with the risk of developing RLF. Even careful monitoring of arterial oxygen tension with serial samples and maintaining the oxygen level between 60 and 100 mm Hg does not guarantee against RLF. Oxygen therapy for premature infants now presents one of those problems of balanced risks which are common throughout the practice of medicine. However, here the balance lies not between tolerable alternatives but rather between two catastrophic end points: death or brain damage from too little oxygen or blindness from too much oxygen. This then is the dilemma faced by the physician treating the high-risk, immature infant. Is the price of intact survival the risk of blindness? Because present technology offers no safe path between these two extremes, the physician must use his best clinical judgment. A number of approaches toward solution of the problem are possible for the future; among these are the development and testing of equipment for continuous monitoring of arterial oxygen tensions, a search for pharmacologic agents to prevent retinal vasoconstriction if exposure to high ambient oxygen concentrations is necessary, the finding of methods to control the onset of labor to diminish the incidence of premature births. There is no way to arrive at any of these solutions other than through research. When alternative risks are as high as in this problem, the necessary clinical research must be planned with extreme care.

Cicatricial retrolental fibroplasia: its occurrence without oxygen administration and in full term infants.

Six patients demonstrating typical signs of the cicatricial phase of retrolental fibroplasia are presented. None of the patients had received supplemental oxygen treatment after birth, and three patients were full term with birth weights ever 6 1/2 pounds. Two of the three premature patients had been born prior to 1901, before the advent of oxygen therapy for premature infants. It is apparent from these observations that retrolental fibroplasia does occur without oxygen administration and also in full term infants.

Commentaries on oxygen therapy I. Oxygen therapy for premature infants: A different approach

Commentaries on oxygen therapy I. Oxygen therapy for premature infants: A different approach

Ophthalmoscopic Monitoring of Oxygen Therapy in Premature Infants: Fluorescein Angiography in Acute Retrolental Fibroplasia

Ophthalmoscopic Monitoring of Oxygen Therapy in Premature Infants: Fluorescein Angiography in Acute Retrolental Fibroplasia

Retinal artery tortuosity in ex-premature infants. 18-year follow-up on eyes of premature infants.

Ophthalmic examinations have been performed on 52 expremature infants who had reached their late teens. These patients all weighed 1500 g or less at birth, and were born during a period of transition from liberal to restricted oxygen therapy for premature infants. Fourteen patients had some degree of retrolental fibrosis. In 4 cases there was complete, bilateral, destructive retrolental fibroplasia (RLF) with microphthalmos; and in 3 cases in which RLF was complete unilaterally, the other eye showed retinal scarring with traction of the disc in 2 patients and extreme tortuosity of the retinal arteries in the third. There were 7 patients who showed bilateral retinal scarring with distortion of the retinal architecture, 35 patients showed tortuosity of the retinal arteries, and 3 patients had normal retinas. It seems that tortuosity of the retinal arteries represents a persistence of the proliferative stage of RLF. In the present study the condition carried no ophthalmic morbidity. Myopia was associated with retrolental scarring, but not with tortuosity of the retinal arteries. Corneal curvature was normal in these patients, excluding this as the cause of the myopia of RLF.

Oxygen therapy for premature infants

I N C R E A S E D oxygen tensions are not encountered in nature. Therefore, it is not surprising that living tissue develops pathologic changes when exposed to high oxygen concentrations. Because of this danger there is a continuing need to devise adequate criteria for the administration of oxygen to newborn infants. Pediatricians are well aware of the difficulties in safely administering oxygen to newborn infants. After World War I I attempts were made to minimize hypoxic injury in premature infants by nursing them in a high ambient oxygen environment; this led to an increased incidence of retrolental fibroplasia. In reaction to this tragedy there followed an era when therapeutic oxygen concentrations were limited to 40 per cent, even in the presence of cyanosis. Some studies have suggested that this policy resulted in an increased mortali ty rate f rom respiratory distress 1 and an increased morbidity rate f rom cerebral palsy? Now, once again, with the development of the concept of neonatal intensive care: higher concentrations of oxygen are being recommended for dyspneic and cyanotic premature infants. With this perhaps more rational approach, new problems are being encountered in the