Hypoxemia In Preterm Infants Research Articles

Stochastic Modeling of Inter-Hypoxemia Intervals in Preterm Infants.

Hypoxemia, characterized by low blood oxygen levels is pervasive in preterm infants and is associated with development of multiple adverse cardiovascular morbidities. In clinical practice, it is often quantified using frequency, pattern and time spent in it. A predictive tool of hypoxemia occurrence will aid clinicians in risk stratifying infant oxygenation patterns and improving personalized care. As a first step towards this goal in characterizing the underlying temporal processes, we studied inter-hypoxemia interval distributions in preterm infants on oxygen supplementation. We derived regression relationships of characterizing parameters of the distributions with gestational age and birth weight of infants. The modeling and goodness of fit tests of pooled and individual inter-hypoxemia intervals indicated that the inverse Gaussian and Birnbaum Saunders distributions fit well over short time scales and the lognormal at longer time scales. Information from distribution modeling may provide insights into hypoxemia recurrence times and be helpful in developing models to predict severe hypoxemic events that may be translated to personalized care in clinical settings. Clinical relevance - Understanding the stochastic nature of temporal processes underlying hypoxemia in preterm infants is a critical step towards developing predictive models for their occurrence. This may potentially aid in the neonatal care and treatment of these vulnerable infants.

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants. Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation. A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56-0.74, all p < 0.01). We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process. · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

Prenatal Opioid Exposure and Intermittent Hypoxemia in Preterm Infants: A Retrospective Assessment.

Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants. In order to accurately calculate IH, SpO2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO2 below 80% (%time-SpO2 < 80). The secondary outcome measure is the number of severe IH events/week with SpO2 less than 80% (IH-SpO2 < 80). A total of 82 infants with isolated opioid exposure (n = 14) or who were unexposed (n = 68) were included. There were no significant differences in baseline characteristics between opioid exposed and unexposed groups. There was a statistically significant increase of 0.23 (95% CI: 0.03, 0.43, p = 0.03) in mean of the square root of %time-SpO2 < 80. The number of IH-SpO2 < 80 events was higher in the opioid exposed group (mean difference = 2.95, 95% CI: -0.35, 6.25, p-value = 0.08), although statistical significance was not quite attained. This study shows that preterm infants prenatally exposed to opioids have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the opioid exposed group persists beyond the immediate postnatal period.

Intermittent Hypoxemia in Preterm Infants: Etiology and Clinical Relevance

Intermittent hypoxemia (IH), episodic drops in hemoglobin oxygen saturation, is a common problem in preterm infants. The extent of IH is not apparent clinically because accurately documenting cardiorespiratory events for day-to-day patient care management is challenging. Multiple factors place preterm infants at high risk for increased IH. These factors include respiratory immaturity, lung disease, and anemia. Brief episodes of oxygen desaturation may seem clinically insignificant; however, these events may have a cumulative effect on neonatal outcomes. There is mounting evidence from both animal models and clinical studies suggesting that IH is associated with injury and poor outcomes such as increased inflammation, impaired growth, retinopathy of prematurity, and neurodevelopmental impairment. In this article, the author reviews the etiology and consequences of IH in preterm infants.

Impact of Caffeine Boluses and Caffeine Discontinuation on Apnea and Hypoxemia in Preterm Infants.

Background: Apnea of prematurity often occurs during and following caffeine therapy. We hypothesized that number of apnea events would be impacted by adjustments in caffeine therapy. Materials and Methods: An automated algorithm was used in all infants ≤32 weeks gestation admitted to a level IV Neonatal Intensive Care Unit from 2009 to 2014 to analyze chest impedance, electrocardiogram, and oxygen saturation data around the time of serum caffeine levels, caffeine boluses while on maintenance therapy, and caffeine discontinuation. Episodes of central apnea/bradycardia/desaturation (ABDs), and percent time with SpO2 <88% and <75% were measured. Results: ABDs were analyzed in 302 preterm infants (mean gestational age 27.6 weeks) around the time of 485 serum caffeine levels, 90 caffeine boluses, and 273 episodes of caffeine discontinuation. Higher serum caffeine levels were not associated with fewer ABDs or higher heart rate. For caffeine boluses given due to clinically recognized spells, hypoxemia and algorithm-detected ABDs decreased day 1-2 after the bolus compared to the day before and day of the bolus (mean 4.4 events/day after vs. 6.6 before, p = 0.004). After caffeine discontinuation, there was no change in hypoxemia and a small increase in ABDs (2 events/day 3-5 days after discontinuation vs. 1 event/day before and >5 days after, p < 0.01). This increase in ABDs occurred irrespective of gestational age, respiratory support, or postmenstrual age at the time caffeine was stopped. Conclusions: In this retrospective analysis, caffeine boluses and caffeine discontinuation were associated with a small change in the number of ABD events in preterm infants.

Apnea of Prematurity.

Apnea of prematurity is one of the most common diagnoses in the NICU. Despite the frequency of apnea of prematurity, it is unknown whether recurrent apnea, bradycardia, and hypoxemia in preterm infants are harmful. Research into the development of respiratory control in immature animals and preterm infants has facilitated our understanding of the pathogenesis and treatment of apnea of prematurity. However, the lack of consistent definitions, monitoring practices, and consensus about clinical significance leads to significant variation in practice. The purpose of this clinical report is to review the evidence basis for the definition, epidemiology, and treatment of apnea of prematurity as well as discharge recommendations for preterm infants diagnosed with recurrent apneic events.

Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants

To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2, independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. ISRCTN 56626482.

Histologic Evidence of Intrapulmonary Anastomoses by Three-Dimensional Reconstruction in Severe Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is the chronic lung disease of infancy that occurs in premature infants after oxygen and ventilator therapy for acute respiratory disease at birth. Despite improvement in current therapies, the clinical course of infants with BPD is often characterized by marked hypoxemia that can become refractory to therapy. Preacinar anatomic and functional communications between systemic and pulmonary vascular systems has been established in fetal lungs, but whether increased intrapulmonary anastomotic vessels or their failure to regress after birth contributes to hypoxemia in preterm infants with BPD is unknown. We sought to find histologic evidence of intrapulmonary anastomotic vessels in lungs of patients who died of severe BPD. We collected lung tissues from fatal BPD cases and performed histology, immunohistochemistry, and high-precision three-dimensional reconstruction techniques. We report histologic evidence of intrapulmonary vessels that bridge pulmonary arteries and veins in the distal lungs of infants dying with severe BPD. These prominent vessels appear similar to "misaligned pulmonary veins" described in the lethal form of congenital lung disorder, alveolar capillary dysplasia. We found striking histological evidence of precapillary arteriovenous anastomotic vessels in the lungs of infants with severe bronchopulmonary dysplasia. We propose that persistence or expansion of these vessels after premature birth provides the anatomic basis for intrapulmonary shunt and hypoxemia in neonates with severe bronchopulmonary dysplasia and may play a significant role in the morbidity and mortality of BPD.

Acute effects of vecuronium on pulmonary function and hypoxemic episodes in preterm infants

Varying effects of pancuronium on neonatal pulmonary mechanics have been documented, including a decrease in pulmonary compliance or no significant change in compliance; but measurements of respiratory mechanics or quantification of episodes of hypoxemia in preterm newborns receiving vecuronium (Norcuron, Bedford Labs, Bedford, OH, USA) have not been reported. The objective of the present study was to quantify the short-term effects of vecuronium on pulmonary mechanics and episodes of hypoxemia in preterm infants receiving mechanical ventilation. A total of 15 preterm infants (birthweight 610-1560 g, gestational age 25-32 weeks, postnatal age 0.2-22 days) was studied. The initial dose of vecuronium used for the study was 0.2 mg/kg i.v. Measurements of respiratory mechanics were obtained 1 h prior to and 1 h after the initial dose of vecuronium at comparable ventilator settings and fractional inspired oxygen concentration (FiO(2)). Dynamic respiratory compliance and respiratory resistance were calculated by two-factor least mean square analysis. Pulse oximeter oxygen saturation (SpO(2)) was measured during both 1 h intervals with the Nellcor N-200 oximeter, a computer, and a software program for quantification of episodes of hypoxemia. Heart rate and blood pressure were also monitored. There were no significant differences in tidal volume, respiratory compliance, or respiratory resistance when comparing measurements obtained before and after vecuronium administration. However, fewer episodes of hypoxemia (SpO(2) < 85%, P = 0.025; and SpO(2) < 80%, P = 0.04) were observed during muscle relaxation. No significant changes in heart rate or blood pressure were noted. The preliminary data indicate: (i) a single dose of vecuronium does not significantly change respiratory compliance or respiratory resistance in preterm infants and (ii) during muscle relaxation fewer episodes of desaturation (hypoxemia) are observed.

Effects of Volume-Targeted Synchronized Intermittent Mandatory Ventilation on Spontaneous Episodes of Hypoxemia in Preterm Infants

Background: Hypoxemic episodes in ventilated preterm infants are frequently caused by reduced ventilation due to a decrease in lung volume and acute worsening of respiratory mechanics. Objective: To compare the efficacy of conventional time-cycled, pressure-limited flow synchronized intermittent mandatory ventilation (SIMV) and volume-targeted SIMV (VT-SIMV) in reducing the frequency and severity of these episodes. Methods: SIMV and VT-SIMV were compared in preterm infants with frequent spontaneous episodes of hypoxemia. VT-SIMV was provided with the Draeger Babylog 8000plus ventilator in volume-guarantee mode. Results: In all, 32 infants (birth weight 668 ± 126 g, gestational age 24.8 ± 1.1 weeks, age 37.5 ± 17.3 days) were studied during 2-hour periods of SIMV and VT-SIMV in random sequence. In an initial phase, a group of 12 infants was supported during VT-SIMV with a target tidal volume of 4.5 ml/kg (VT-SIMV 4.5). A planned interim analysis did not show differences in frequency and duration of hypoxemia between VT-SIMV 4.5 and SIMV, and the initial phase was stopped. In a second phase of the study, 20 infants were studied while supported with a target tidal volume of 6.0 ml/kg during VT-SIMV (VT-SIMV 6.0). In the second phase of the study, the frequency of the hypoxemic episodes did not change but the mean episode duration was shorter during VT-SIMV compared to SIMV. The proportion of mechanical breaths with small tidal volumes (≤3 ml/kg) was reduced during VT-SIMV 6.0 versus SIMV, while the peak inspiratory pressure and mean airway pressure were increased. Conclusion: VT-SIMV did not reduce the frequency of hypoxemic episodes, but VT-SIMV 6.0 was effective in reducing the duration of the hypoxemic episodes.

Pulmonary Hypertension and Right Ventricular Dysfunction in Growth-Restricted, Extremely Low Birth Weight Neonates

This case series reports an acute episode of hypoxemia and systemic hypotension in seven infants under 1 kg, taking place several hours or days after birth, after a period of stability and in the absence of significant lung disease. These patients were growth-restricted at birth and had a history of chronic fetal hypoxia and oligohydramnios. Pulmonary hypertension and right ventricular dysfunction were found by echocadiography. Right ventricular ejection fraction was significantly depressed during the acute episode, compared to baseline values measured after recovery. The timing of symptoms seemed related to ductus arteriosus closure or constriction. Oxygenation and right ventricular function improvement occurred within a few days under ventilatory and inotropic support, while milrinone was administered in five cases. In conclusion, pulmonary hypertension is a rare but significant cause of hypoxemia in preterm infants, and pulmonary vasodilator therapy should be considered in the presence of right ventricular dysfunction.

Efficacy and safety of tolazoline for treatment of severe hypoxemia in extremely preterm infants.

To determine the efficacy of tolazoline as a rescue treatment for hypoxemia in preterm infants with respiratory distress syndrome. Retrospective chart review on case series of infants weighing < 750 g at birth who received tolazoline during a severe hypoxemic episode while receiving maximal ventilator support for respiratory distress syndrome. A slow bolus infusion of low dose tolazoline (0.5 mg-2 mg/kg) mixed with plasmanate or normal saline (10 mL/kg) was administered. Outcome measures evaluated included an increase in PaO(2) > or =20 mm Hg from pretreatment value and an increase in oxygen saturation to > or =90%. Forty-three infants with a mean gestational age and birth weight of 24 weeks and 581 g, respectively, received tolazoline. All infants were mechanically ventilated and required a fraction of inspired oxygen of 1.0. Oxygenation improved in 72% (31/43) of infants with a tolazoline dose of 0.5 to 1.0 mg/kg. Of those who responded, PaO(2) values (mean +/- standard deviation) pretolazoline and posttolazoline were 32 +/- 7.5 mm Hg and 156 +/- 114.9 mm Hg, respectively. In all responders, oxygen saturation increased to > or =90% within 30 minutes of tolazoline administration. Improvement in pH, pCO(2), oxygenation index, and mean airway pressure was also noted. Among nonresponders, pH decreased and pCO(2) increased after tolazoline. Minimal change in blood pressure was noted in both responders and nonresponders. Heart rate decreased by 19 beats per minute among nonresponders compared with an increase of 3 beats per minute in those who responded to tolazoline. Tolazoline is an effective treatment of severe resistant hypoxemia in preterm infants who are already on vigorous ventilatory support.

Regional Cerebral Blood Flow During Hypotension and Hypoxemia in Preterm Infants 28

Introduction: Periventricular leucomalacia (PVL) is hypothesized to be due to an impaired autoregulation leading to ischemia of the periventricular white matter. The aim of this study was to examine if hypotension or hypoxemia leads to a relatively decreased blood flow to the cerebral white matter in preterm infants.

Effect of Blood Transfusion on Apnea, Bradycardia and Hypoxemia in Preterm Infants 197

Objective: To study the effect of blood transfusion on the frequency of apnea, bradycardia and hypoxemia. Patients: 21 spontaneously breathing preterm infants, median GA at birth 28 (range 23.31) wk, age at study 22 d (3.84), weight at study 925 g (640-2120), who exhibited frequent episodes of bradycardia and/or hypoxemia and were anemic (median hemoglobin level 109 (82-120) g/l). Methods: 4 h recordings of pulse oximeter saturation (SpO2), pulse waveforms, ECG, breathing movements and nasal airflow immediately before and after transfusion, and again after a further interval of 12 h. Analysis of recordings for isolated and periodic apneas (>4 s), bradycardias (heart rate <2/3 of baseline), and episodic desaturation (SpO2 ≤80%). Results: There were no significant changes in the frequency of apnea, bradycardia or desaturation following transfusion. There was also no significant change in the severity and/or duration of apnea or bradycardia. The average SpO2 nadir reached during each desaturation, however, increased by 3% following transfusion (p<0.05), and there was a trend towards shorter desaturations. Conclusion: There was no clinically significant effect of blood transfusion on apnea, bradycardia or hypoxemia in these relatively young and mildly anemic preterm infants. These data suggest that the occurrence of frequent episodes of apnea, bradycardia and/or hypoxemia does not, on its own, justify a blood transfusion in mildly anemic preterm infants.

Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation

Objective: To ascertain possible mechanisms implicated in the development of transient episodes of hypoxemia (oxygen saturation <85%) frequently observed in preterm infants undergoing mechanical ventilation, even after the acute phase of respiratory failure has passed. Study design: Tidal flow, airway and esophageal pressure, and oxygen saturation were continuously recorded in 10 infants (mean ± SD, birth weight 733 ± 149 gm, gestational age 25.5 ± 2.2 weeks, age 26.3 ± 11.9 days) who had repeated episodes of hypoxemia without any evident cause. Measurements of minute ventilation (v̇ E), inspiratory compliance (C i), and inspiratory resistance (R i) were compared before and during episodes of hypoxemia. Results: All episodes of hypoxemia were preceded by an active exhalation that produced a mean decrease in end-expiratory lung volume of 6.4 ± 2.8 ml/kg. The reduction in lung volume was immediately followed by a sudden decrease in tidal flow and volume, despite continuation of mechanical ventilation at the same rate and peak pressure. The resulting hypoventilation was associated with a drop in C i to approximately one half and an increase in R i to more than double the baseline values. Approximately 30 seconds after the beginning of hypoventilation, the arterial oxygen saturation reached a hypoxemic level (oxygen saturation <85%). Conclusion: Most hypoxemic episodes were triggered by an expiratory effort that produced a large decrease in lung volume. This reduction in lung volume probably leads to closure of small airways and the development of intrapulmonary shunts, which would explain the rapid development of hypoxemia. (J P EDIATR 1995;127:767-73)

The relationship between bradycardia, apnea, and hypoxemia in preterm infants.

The pathogenesis of bradycardias in preterm infants is poorly understood. Because their pathogenesis may involve both apnea and hypoxemia, we set out to analyze the proportion of bradycardias that were associated with an apneic pause and/or a fall in arterial oxygen saturation (SaO2), and the temporal sequence of the three phenomena, in overnight tape recordings of SaO2 (Nellcor N100 in beat-to-beat mode), breathing movements, nasal airflow, and ECG in 80 preterm infants at the time of discharge from hospital. A bradycardia was defined as a fall in heart rate of > or = 33% from baseline for > or = 4 s, an apneic pause as a cessation of breathing movements and/or airflow for > or = 4 s, and a desaturation as a fall in SaO2 to < or = 80%. A total of 193 bradycardias were found in 46 (58%) of the recordings (median, three per recording; range 1-18). There was a close relationship between bradycardias, apneic pauses, and desaturations: 83% of bradycardias were associated with apneic pauses and 86% with desaturations. Where all three phenomena occurred in combination, the time from the onset of apnea to the onset of the fall in SaO2 was shorter (median interval, 0.8 s; range -4.9-+ 11.5 s) than that from the onset of apnea to the onset of bradycardia (median, 4.8 s; range -4.0-+ 14.0 s). Hence, most bradycardias (86%) commenced after the onset of the fall in SaO2. We conclude that bradycardia, apnea, and hypoxemia are closely linked phenomena in preterm infants.

Arterial oxygen saturation in preterm infants at discharge from the hospital and six weeks later

To obtain normal data on arterial oxygen saturation (SaO2) in preterm infants and to study early developmental changes in SaO2, we obtained overnight tape recordings of SaO2 and breathing movements in 160 preterm infants at their discharge from three special care baby units (mean gestational age at birth 33 weeks; at time of study, 37 weeks). One hundred ten infants (69%) underwent a second recording 6 weeks later. Median baseline SaO2 during regular breathing was 99.5% (range 88.7% to 100%) at discharge, and 100% (range 95.3% to 100%) at follow-up (p less than 0.001). The number of episodes of desaturation, defined as a fall in SaO2 to less than or equal to 80% for at least 4 seconds, corrected to the mean duration of recording (12.2 hours), decreased from a median of 3 (0 to 355) to 0 (0 to 17) (p less than 0.001). The median duration of each episode of desaturation remained unchanged (5.2 (4.0 to 22.7) vs 5.5 (4.2 to 24.0) seconds). At discharge, a small minority of infants had a clinically unrecognized low baseline SaO2 (lowest, 88.7%; 5th percentile, 95.7%) or a high number of desaturation episodes (the highest was six times the 95th percentile value). At follow-up, all outlying values had normalized. Follow-up recordings made between 42 and 47 weeks of gestational age (n = 53) were compared with similar recordings from 67 term infants at the same gestational age. The preterm infants had a significantly higher baseline SaO2 and no more desaturation than the infants born at term. Knowledge of normal ranges of oxygenation and their changes with age may be of value in identifying clinically undetected hypoxemia in preterm infants at discharge from the hospital. The potential influence of such hypoxemia on clinical outcome remains to be determined.

Airway closure in children.

Airway closure in children.