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Richard Harding - One of the best experts on this subject based on the ideXlab platform.

  • fetal brain injury following prolonged Hypoxemia and placental insufficiency a review
    Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 1998
    Co-Authors: Sandra Rees, Carina Mallard, Sibilah Breen, M Stringer, Megan L Cock, Richard Harding
    Abstract:

    Abstract It is well-established that severe, acute episodes of Hypoxemia can damage the brain before birth, but the effects of more sustained Hypoxemia are less well understood. We have used fetal sheep in a series of studies aimed at determining the effects of prolonged Hypoxemia, induced by placental insufficiency of differing severity and duration, on fetal brain structure. Restriction of placental, and hence fetal, growth by carunclectomy caused impaired development of neural processes and connections in the hippocampus, cerebellum, and visual cortex; neuronal migration and neuronal numbers did not appear to be affected. Twenty days of placental insufficiency during late gestation induced by umbilicoplacental embolisation also caused abnormalities in brain structure; the cerebellum, which develops late in gestation, was particularly affected. In the cortex, there was evidence of white matter lesions, an increase in the size of capillaries and a proliferation of astroglia. We also examined the effects of shorter periods of Hypoxemia (6–12 hr) near mid-gestation on brain structure; fetuses were allowed to recover for 7 or 35 days after the hypoxemic challenge. The major changes were mild focal damage in the cortical white matter, a reduction in the number of Purkinje cells, a delay in the growth of neural processes in the cerebellum and proliferation of blood vessels. The hippocampus was also affected, in particular the areal density of pyramidal cells was reduced. The use of several classes of pharmacological agents with the potential to protect neurons from hypoxemic injury is discussed in relation to the developing brain.

  • Effects of Chronic Placental Insufficiency on Brain Development in Fetal Sheep
    Pediatric Research, 1998
    Co-Authors: E Carina Mallard, M Stringer, Sandra Rees, Megan L Cock, Richard Harding
    Abstract:

    Clinical evidence has linked intrauterine compromise such as fetal Hypoxemia to poor neurologic outcome in the newborn. In this study we examined the effects of inducing chronic fetal Hypoxemia by impairment of placental function on brain development in fetal sheep. Placental insufficiency was induced from 120 to 140 d of gestation (term = 145-148 d) by injection of microspheres into the umbilical circulation in five fetal sheep. Fetal partial pressure of oxygen, Pao_2, was reduced from 24.1 ± 0.5 mm Hg before embolization to 14.8 ± 0.4 mm Hg after embolization ( p < 0.05). In another three fetuses a similar level of Hypoxemia(Pao_2, 13.8 ± 0.4 mm Hg) occurred spontaneously. At 140 d of gestation the fetal brains were perfused with fixatives and compared with five control fetuses for the assessment of structural and immunohistochemical alterations. Hypoxemic fetuses demonstrated severe gliosis in the cerebral cortex and reduced myelination of subcortical white matter as visualized by glial fibrillary acidic protein and myelin basic protein staining, respectively ( p < 0.05). White matter lesions were observed in two fetuses. The diameter of cerebral capillaries was increased in hypoxemic fetuses ( p < 0.05), but there was no change in the number of nitric oxide synthase immunoreactive cells. Growth of neuronal processes was affected in the cerebellum, where there was also a reduction in the number of Purkinje neurons ( p < 0.05). These results show that a prolonged period of placental insufficiency, resulting in moderate fetal Hypoxemia during the last third of gestation, can affect neurodevelopmental processes that occur late in gestation such as myelination and growth of the cerebellum. This prenatal damage could affect neural connectivity and have functional consequences after birth.

Henrietta S. Bada - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety of tolazoline for treatment of severe Hypoxemia in extremely preterm infants
    Pediatrics, 2002
    Co-Authors: Pracha Nuntnarumit, Wenjian Yang, S B Korones, Henrietta S. Bada
    Abstract:

    Objective. To determine the efficacy of tolazoline as a rescue treatment for Hypoxemia in preterm infants with respiratory distress syndrome. Methods. 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 ≥20 mm Hg from pretreatment value and an increase in oxygen saturation to ≥90%. Results. 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 ≥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. Conclusion. Tolazoline is an effective treatment of severe resistant Hypoxemia in preterm infants who are already on vigorous ventilatory support. Pediatrics 2002; 109:852-856; respiratory distress syndrome, pulmonary hypertension, Hypoxemia, premature, newborn.

Eddy Fan - One of the best experts on this subject based on the ideXlab platform.

  • outcome of acute hypoxaemic respiratory failure insights from the lung safe study
    European Respiratory Journal, 2020
    Co-Authors: Tai Pham, Eddy Fan, Antonio Pesenti, Giacomo Bellani, Gordon D Rubenfeld, Guillermo Bugedo, Jose A Lorente, Antero Fernandes
    Abstract:

    Background The current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in intensive care unit are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). Methods An international, multicentre, prospective cohort study of patients presenting with Hypoxemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with PaO2/FiO2 ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure (PEEP) of at least 5 cm H2O. ICU prevalence, causes of Hypoxemia, hospital survival, factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. Findings 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (8.2%, CHF). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1%versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality but similar adjusted mortality than ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only 2 quadrants involved. Interpretation More than one third of the patients receiving mechanical ventilation have hypoxaemia and new infiltrates with an hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

  • therapies for refractory Hypoxemia in acute respiratory distress syndrome
    JAMA, 2010
    Co-Authors: Matthew R Pipeling, Eddy Fan
    Abstract:

    Acute respiratory distress syndrome (ARDS) is a common and severe form of acute lung injury, resulting from both direct (eg, pneumonia) and indirect (eg, sepsis) pulmonary insults. It is a common cause of admission to the intensive care unit due to hypoxemic respiratory failure requiring mechanical ventilation, and is associated with significant morbidity and mortality. In some patients, ARDS leads to the development of life-threatening refractory Hypoxemia. In these patients, physicians may consider a number of therapies (eg, recruitment maneuvers, prone positioning, inhaled nitric oxide, high-frequency oscillatory ventilation, extracorporeal membrane oxygenation) to alleviate Hypoxemia in patients unable to maintain reasonable oxygenation while being supported with conventional mechanical ventilation. Although these strategies have demonstrated improved oxygenation with their use, their impact on patient-important outcomes (eg, mortality) remains unproven. However, in the minority of patients with ARDS and refractory Hypoxemia, institution of these therapies may be considered on a case-by-case basis. Future studies are needed to elucidate the efficacy of these therapies on outcomes in patients with severe ARDS and refractory Hypoxemia.

Dev Banerjee - One of the best experts on this subject based on the ideXlab platform.

  • the potential association between obstructive sleep apnea and diabetic retinopathy in severe obesity the role of Hypoxemia
    PLOS ONE, 2013
    Co-Authors: Dev Banerjee, Wen Bun Leong, Teresa Arora, Melissa Nolen, Vikas Punamiya, Ronald R Grunstein, Shahrad Taheri
    Abstract:

    BACKGROUND Obstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications. METHODS To investigate the association between OSA, Hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m(2)) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA-). RESULTS Forty-six patients were OSA+: median (95% CI) AHI = 37(23-74)/hour and 47 were OSA-ve (AHI = 7(4-11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA- groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65-0.95; p<0.05), after adjustment. CONCLUSIONS The presence of OSA, as determined by AHI, was not associated with diabetic retinal complications. In contrast, severity of Hypoxemia during sleep (minimum oxygen saturations) may be an important factor. The importance of hypoxia in the development of retinal complications in patients with OSA remains unclear and further studies assessing the pathogenesis of Hypoxemia in patients with OSA and diabetic retinal disease are warranted.

Barbara Schmidt - One of the best experts on this subject based on the ideXlab platform.

  • association between intermittent Hypoxemia and severe bronchopulmonary dysplasia in preterm infants
    American Journal of Respiratory and Critical Care Medicine, 2021
    Co-Authors: Erik A Jensen, Barbara Schmidt, Robin K Whyte, Dirk Bassler, Nestor E Vain, Robin S Roberts
    Abstract:

    RATIONALE Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent Hypoxemia may play a role in this relationship. OBJECTIVE To determine the association between prolonged episodes of intermittent Hypoxemia and severe bronchopulmonary dysplasia. METHODS Post-hoc analysis of extremely preterm infants in the Canadian Oxygen Trial who survived to 36 weeks postmenstrual age. Oxygen saturations <80% for ≥1 minute and the proportion of time per day with Hypoxemia were quantified using continuous pulse oximetry data that had been sampled every 10 seconds from within 24 hours of birth until 36 weeks postmenstrual age. The study outcome was severe bronchopulmonary dysplasia as defined in the 2001 National Institutes of Health Workshop Summary. RESULTS Of 1018 infants, 332 (32.6%) developed severe bronchopulmonary dysplasia. The median number of hypoxemic episodes ranged from 0.8/day (IRQ 0.2-1.1) to 60.2/day (IQR 51.4-70.3) among the least and most affected 10% of infants. Compared to the lowest decile of exposure to hypoxemic episodes, the adjusted relative risk of severe bronchopulmonary dysplasia increased progressively from 1.72 (95% CI 1.55-1.90) at the second decile to 20.40 (95% CI 12.88-32.32) at the 10th decile. Similar risk gradients were observed for time in Hypoxemia. Significant differences in the rates of Hypoxemia between infants with and without severe bronchopulmonary dysplasia emerged within the first week after birth. CONCLUSIONS Prolonged intermittent Hypoxemia beginning in the first week after birth was associated with an increased risk of developing severe bronchopulmonary dysplasia among extremely preterm infants.

  • association between intermittent Hypoxemia or bradycardia and late death or disability in extremely preterm infants
    JAMA, 2015
    Co-Authors: Christian F Poets, Robin S Roberts, Barbara Schmidt, Robin K Whyte, Elizabeth Asztalos, David Bader, Aida Bairam, Diane Moddemann, Abraham Peliowski
    Abstract:

    Importance Extremely preterm infants may experience intermittent Hypoxemia or bradycardia for many weeks after birth. The prognosis of these events is uncertain. Objective To determine the association between intermittent Hypoxemia or bradycardia and late death or disability. Design, Setting, and Participants Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks. Follow-up assessments occurred between October 2008 and August 2012. Exposures Episodes of Hypoxemia (pulse oximeter oxygen saturation Main Outcomes and Measures The primary outcome was a composite of death after 36 weeks’ postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months’ corrected age. Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity. Results Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0 days). Mean percentages of recorded time with Hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively. Corresponding values for bradycardia were 0.1% and 0.3%. The primary outcome was ascertained for 972 infants and present in 414 (42.6%). Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94). This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05 vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32). Relative risks for all secondary outcomes were similarly increased after prolonged Hypoxemia. Bradycardia did not alter the prognostic value of Hypoxemia. Conclusions and Relevance Among extremely preterm infants who survived to 36 weeks’ postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes. If confirmed in future studies, further research on the prevention of such episodes is needed.