Faster resolution of hypoxaemic or hyperoxaemic events in preterm infants may reduce long-term neurodevelopmental impairment. Automatic titration of inspiratory oxygen increases time within the... Show moreFaster resolution of hypoxaemic or hyperoxaemic events in preterm infants may reduce long-term neurodevelopmental impairment. Automatic titration of inspiratory oxygen increases time within the oxygen saturation target range and may provide a more prompt response to hypoxic and hyperoxic events. We assessed routinely performed follow-up at 2 years of age after the implementation of automated oxygen control (AOC) as standard care and compared this with a historical cohort. Neurodevelopmental outcomes at 2 years of age were compared for infants born at 24-29 weeks gestational age before (2012-2015) and after (2015-2018) the implementation of AOC as standard of care. The primary outcome was a composite outcome of either mortality or severe neurodevelopmental impairment (NDI), and other outcomes assessed were mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and CBCL problem behaviour scores. A total of 289 infants were included in the pre-AOC epoch and 292 in the post-AOC epoch. Baseline characteristics were not significantly different. Fifty-one infants were lost to follow-up (pre-AOC 6.9% (20/289), post-implementation 10.6% (31/292). The composite outcome of mortality or severe NDI was observed in 17.9% pre-AOC (41/229) vs. 24.0% (47/196) post-AOC (p = 0.12). No significant differences were found for the secondary outcomes such as mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and problem behaviour scores, with the exception of parent-reported readmissions until the moment of follow-up which was less frequent post-AOC than pre-AOC.Conclusion: In this cohort study, the implementation of automated oxygen control in our NICU as standard of care for preterm infants led to no statistically significant difference in neurodevelopmental outcome at 2 years of age. Show less
Most preterm infants need respiratory support and extra oxygen during their admission to the neonatal intensive care. The amount of oxygen required can fluctuate a lot. Bedside staff frequently... Show moreMost preterm infants need respiratory support and extra oxygen during their admission to the neonatal intensive care. The amount of oxygen required can fluctuate a lot. Bedside staff frequently administer extra oxygen, and when the blood oxygen level is normalised, reduce this extra oxygen carefully. This is a delicate process, a fraction too much or a fraction too little may harm their underdeveloped organs.As one of the first, the LUMC has been titrating oxygen automatically since 2015. In this thesis we investigated the effect of this automatization and how preterm infants can profit from this technology. We found that automated oxygen titration reduced the duration of invasive ventilation, but outcome at two years of age was left unchanged. A new automated oxygen controller from 2018 led to even more improvement. Infants spent more time in the narrow therapeutic range, needed even less intensive respiratory support and developed less retinopathy – a disease of the retina which, when untreated, can lead to blindness.From this thesis we can conclude that there is a short-term benefit from automated oxygen titration and we are moving in the right direction. Further research is needed to make the most out of this technology. Show less
Salverda, H.H.; Oldenburger, N.J.; Rijken, M.; Pauws, S.C.; Dargaville, P.A.; Pas, A.B. te 2021
Several studies demonstrated an increase in time spent within target range when automated oxygen control (AOC) is used. However the effect on clinical outcome remains unclear. We compared clinical... Show moreSeveral studies demonstrated an increase in time spent within target range when automated oxygen control (AOC) is used. However the effect on clinical outcome remains unclear. We compared clinical outcomes of preterm infants born before and after implementation of AOC as standard of care. In a retrospective pre-post implementation cohort study of outcomes for infants of 24-29 weeks gestational age receiving respiratory support before (2012-2015) and after (2015-2018) implementation of AOC as standard of care were compared. Outcomes of interest were mortality and complications of prematurity, number of ventilation days, and length of stay in the Neonatal Intensive Care Unit (NICU). A total of 588 infants were included (293 pre- vs 295 in the post-implementation cohort), with similar gestational age (27.8 weeks pre- vs 27.6 weeks post-implementation), birth weight (1033 grams vs 1035 grams) and other baseline characteristics. Mortality and rate of prematurity complications were not different between the groups. Length of stay in NICU was not different, but duration of invasive ventilation was shorter in infants who received AOC (6.4 +/- 10.1 vs 4.7 +/- 8.3, p = 0.029). Conclusion: In this pre-post comparison, the implementation of AOC did not lead to a change in mortality or morbidity during admission.What is Known:Prolonged and intermittent oxygen saturation deviations are associated with mortality and prematurity-related morbidities.Automated oxygen controllers can increase the time spent within oxygen saturation target range.What is New:Implementation of automated oxygen control as standard of care did not lead to a change in mortality or morbidity during admission.In the period after implementation of automated oxygen control, there was a shift toward more non-invasive ventilation. Show less
The side-effects of hyperoxia can be roughly subdivided in cell damage, inflammation, pulmonary complications, neurological symptoms and vascular effects. These features are responsible for the... Show moreThe side-effects of hyperoxia can be roughly subdivided in cell damage, inflammation, pulmonary complications, neurological symptoms and vascular effects. These features are responsible for the large majority of unfavourable effects and increased risk for morbidity and mortality following (prolonged) exposure to hyperoxia. From this thesis, we conclude that careful oxygen titration and monitoring is the best therapeutic strategy aimed at the prevention of potentially dangerous hyperoxia while preserving adequate tissue oxygenation. In this context, conservative oxygenation in the intensive care unit is a promising strategy to achieve better clinical outcomes for critically ill patients. Administering oxygen remains essential to prolong the window of opportunity and provide as much oxygen as necessary in anticipation of or during arterial hypoxia, and to rapidly establish pulmonary vasodilation or systemic vasoconstriction, when other measures are inadequate or fail. At the same time, clinicians should be well aware of the side-effects that are induced by supplying high levels of oxygen, as hyperoxia is also frequently encountered in critically ill patients.In expectation of compelling evidence from future clinical trials, targeting relative normoxia (80-150 mmHg) by avoiding exposure to both subphysiological as well as supraphysiological oxygenation should be considered the most rational choice in most patients. Show less
Due to a lack of patient materials and ethical reasons animal models of BPD are critical for characterization the pathophysiology of BPD and testing of potential treatment options. In chapter 2 of... Show moreDue to a lack of patient materials and ethical reasons animal models of BPD are critical for characterization the pathophysiology of BPD and testing of potential treatment options. In chapter 2 of this thesis we characterize a rat model for experimental BPD, induced in neonatal pups by prolonged exposure to hyperoxia, by investigating histopathology and differential gene expression profiles in the lung and demonstrate its significance for studying BPD in premature infants. In chapter 3 we describe the spatial and temporal expression of surfactant proteins in this experimental BPD model. Since inflammation and unbalanced coagulation and fibrinolysis, leading to extravascular fibrin deposition in the lung, are two interrelated processes that play a pivotal role in the pathophysiology of inflammatory lung disease, we investigated whether the pathophysiology of experimental BPD could be improved by interrupting the vicious cycle of inflammation and coagulation. Fibrin deposition can be prevented directly via inhibition of the coagulation cascade and/or stimulation of the fibrinolytic cascade or indirectly via inhibition of the inflammatory response, thereby preventing activated leucocytes to perform their procoagulant and antifibrinolytic activity. In chapters 4 and 5 intervention studies in experimental BPD are described which study the potential therapeutic effect of agents with anti-inflammatory and/or anticoagulant activity for premature infants who are at risk of developing BPD. The role of pentoxifylline, a methylxantine derivative and weak non-selective phosphodiesterase inhibitor with anti-inflammatory and anticoagulant properties, and with positive effects on capillary blood flow in experimental BPD is presented in chapter 4. The role of nitric oxide, a gas that is involved in multiple (patho)physiological processes in the injured lung, including pulmonary vasodilatation, inflammation and plasma exudation, is presented in chapter 5. In chapter 6 the presented studies of chapters 2-5 and the future perspectives are discussed. In chapter 7 a summary is given of this thesis. Due to a lack of patient materials and ethical reasons animal models of BPD are critical for characterization the pathophysiology of BPD and testing of potential treatment options. In chapter 2 of this thesis we characterize a rat model for experimental BPD, induced in neonatal pups by prolonged exposure to hyperoxia, by investigating histopathology and differential gene expression profiles in the lung and demonstrate its significance for studying BPD in premature infants. In chapter 3 we describe the spatial and temporal expression of surfactant proteins in this experimental BPD model. Since inflammation and unbalanced coagulation and fibrinolysis, leading to extravascular fibrin deposition in the lung, are two interrelated processes that play a pivotal role in the pathophysiology of inflammatory lung disease, we investigated whether the pathophysiology of experimental BPD could be improved by interrupting the vicious cycle of inflammation and coagulation. Fibrin deposition can be prevented directly via inhibition of the coagulation cascade and/or stimulation of the fibrinolytic cascade or indirectly via inhibition of the inflammatory response, thereby preventing activated leucocytes to perform their procoagulant and antifibrinolytic activity. In chapters 4 and 5 intervention studies in experimental BPD are described which study the potential therapeutic effect of agents with anti-inflammatory and/or anticoagulant activity for premature infants who are at risk of developing BPD. The role of pentoxifylline, a methylxantine derivative and weak non-selective phosphodiesterase inhibitor with anti-inflammatory and anticoagulant properties, and with positive effects on capillary blood flow in experimental BPD is presented in chapter 4. The role of nitric oxide, a gas that is involved in multiple (patho)physiological processes in the injured lung, including pulmonary vasodilatation, inflammation and plasma exudation, is presented in chapter 5. In chapter 6 the presented studies of chapters 2-5 and the future perspectives are discussed. In chapter 7 a summary is given of this thesis. Due to a lack of patient materials and ethical reasons animal models of BPD are critical for characterization the pathophysiology of BPD and testing of potential treatment options. In chapter 2 of this thesis we characterize a rat model for experimental BPD, induced in neonatal pups by prolonged exposure to hyperoxia, by investigating histopathology and differential gene expression profiles in the lung and demonstrate its significance for studying BPD in premature infants. In chapter 3 we describe the spatial and temporal expression of surfactant proteins in this experimental BPD model. Since inflammation and unbalanced coagulation and fibrinolysis, leading to extravascular fibrin deposition in the lung, are two interrelated processes that play a pivotal role in the pathophysiology of inflammatory lung disease, we investigated whether the pathophysiology of experimental BPD could be improved by interrupting the vicious cycle of inflammation and coagulation. Fibrin deposition can be prevented directly via inhibition of the coagulation cascade and/or stimulation of the fibrinolytic cascade or indirectly via inhibition of the inflammatory response, thereby preventing activated leucocytes to perform their procoagulant and antifibrinolytic activity. In chapters 4 and 5 intervention studies in experimental BPD are described which study the potential therapeutic effect of agents with anti-inflammatory and/or anticoagulant activity for premature infants who are at risk of developing BPD. The role of pentoxifylline, a methylxantine derivative and weak non-selective phosphodiesterase inhibitor with anti-inflammatory and anticoagulant properties, and with positive effects on capillary blood flow in experimental BPD is presented in chapter 4. The role of nitric oxide, a gas that is involved in multiple (patho)physiological processes in the injured lung, including pulmonary vasodilatation, inflammation and plasma exudation, is presented in chapter 5. In chapter 6 the presented studies of chapters 2-5 and the future perspectives are discussed. In chapter 7 a summary is given of this thesis. Due to a lack of patient materials and ethical reasons animal models of BPD are critical for characterization the pathophysiology of BPD and testing of potential treatment options. In chapter 2 of this thesis we characterize a rat model for experimental BPD, induced in neonatal pups by prolonged exposure to hyperoxia, by investigating histopathology and differential gene expression profiles in the lung and demonstrate its significance for studying BPD in premature infants. In chapter 3 we describe the spatial and temporal expression of surfactant proteins in this experimental BPD model. Since inflammation and unbalanced coagulation and fibrinolysis, leading to extravascular fibrin deposition in the lung, are two interrelated processes that play a pivotal role in the pathophysiology of inflammatory lung disease, we investigated whether the pathophysiology of experimental BPD could be improved by interrupting the vicious cycle of inflammation and coagulation. Fibrin deposition can be prevented directly via inhibition of the coagulation cascade and/or stimulation of the fibrinolytic cascade or indirectly via inhibition of the inflammatory response, thereby preventing activated leucocytes to perform their procoagulant and antifibrinolytic activity. In chapters 4 and 5 intervention studies in experimental BPD are described which study the potential therapeutic effect of agents with anti-inflammatory and/or anticoagulant activity for premature infants who are at risk of developing BPD. The role of pentoxifylline, a methylxantine derivative and weak non-selective phosphodiesterase inhibitor with anti-inflammatory and anticoagulant properties, and with positive effects on capillary blood flow in experimental BPD is presented in chapter 4. The role of nitric oxide, a gas that is involved in multiple (patho)physiological processes in the injured lung, including pulmonary vasodilatation, inflammation and plasma exudation, is presented in chapter 5. In chapter 6 the presented studies of chapters 2-5 and the future perspectives are discussed. In chapter 7 a summary is given of this thesis. Show less
