Inspiratory Fraction Research Articles

Oxygen Therapy: Systems and Indications in the Pediatric and Adult Population

Hypoxemia is defined as the decrease in arterial partial pressure of oxygen (PaO2) below 80 mmHg. One of the ways to alleviate this condition is through oxygen therapy, which consists of administering oxygen at a concentration higher than atmospheric. This therapy is indicated in various pathologies and is aimed to treat hypoxemia and reduce the patient's myocardial demand and respiratory effort. Classically, this treatment has been carried out using low-flow systems, in which the inspiratory fraction of oxygen (FiO2) cannot be regulated. However, an increase in the use of high-flow oxygen therapy (HFO) has been observed in recent years. These systems allow for greater patient comfort as well as more precise regulation of the FiO2. The purpose of this article is to review respiratory physiology to understand respiratory failure from a clinical and pathophysiological point of view. Likewise, the different oxygen therapy systems most widely used are discussed, as well as their indications for acute and chronic pathologies, both in the pediatric and adult populations.

Static and Dynamic Contributors to Ventilator-induced Lung Injury in Clinical Practice. Pressure, Energy, and Power.

Ventilation is inherently a dynamic process. The present-day clinical practice of concentrating on the static inflation characteristics of the individual tidal cycle (plateau pressure, positive end-expiratory pressure, and their difference [driving pressure, the ratio of Vt to compliance]) does not take into account key factors shown experimentally to influence ventilator-induced lung injury (VILI). These include rate of airway pressure change (influenced by flow amplitude, inspiratory time fraction, and inspiratory inflation contour) and cycling frequency. Energy must be expended to cause injury, and the product of applied stress and resulting strain determines the energy delivered to the lungs per breathing cycle. Understanding the principles of VILI energetics may provide valuable insights and guidance to intensivists for safer clinical practice. In this interpretive review, we highlight that the injuring potential of the inflation pattern depends upon tissue vulnerability, the number of intolerable high-energy cycles applied in unit time (mechanical power), and the duration of that exposure. Yet, as attractive as this energy/power hypothesis for encapsulating the drivers of VILI may be for clinical applications, we acknowledge that even these all-inclusive and measurable ergonomic parameters (energy per cycle and power) are still too bluntly defined to pinpoint the precise biophysical link between ventilation strategy and tissue injury.

Effects of variable versus nonvariable controlled mechanical ventilation on pulmonary inflammation in experimental acute respiratory distress syndrome in pigs

BackgroundMechanical ventilation with variable tidal volumes (VT) may improve lung function and reduce ventilator-induced lung injury in experimental acute respiratory distress syndrome (ARDS). However, previous investigations were limited to less than 6 h, and control groups did not follow clinical standards. We hypothesised that 24 h of mechanical ventilation with variable VT reduces pulmonary inflammation (as reflected by neutrophil infiltration), compared with standard protective, nonvariable ventilation. MethodsExperimental ARDS was induced in 14 anaesthetised pigs with saline lung lavage followed by injurious mechanical ventilation. Pigs (n=7 per group) were randomly assigned to using variable VT or nonvariable VT modes of mechanical ventilation for 24 h. In both groups, ventilator settings including positive end-expiratory pressure and oxygen inspiratory fraction were adjusted according to the ARDS Network protocol. Pulmonary inflammation (primary endpoint) and perfusion were assessed by positron emission tomography using 2-deoxy-2-[18F]fluoro-d-glucose and 68Gallium (68Ga)-labelled microspheres, respectively. Gas exchange, respiratory mechanics, and haemodynamics were quantified. Lung aeration was determined using CT. ResultsThe specific global uptake rate of 18F-FDG increased to a similar extent regardless of mode of mechanical ventilation (median uptake for variable VT=0.016 min−1 [inter-quartile range, 0.012–0.029] compared with median uptake for nonvariable VT=0.037 min−1 [0.008–0.053]; P=0.406). Gas exchange, respiratory mechanics, haemodynamics, and lung aeration and perfusion were similar in both variable and nonvariable VT ventilatory modes. ConclusionIn a porcine model of ARDS, 24 h of mechanical ventilation with variable VT did not attenuate pulmonary inflammation compared with standard protective mechanical ventilation with nonvariable VT.

A lung rescue team improves survival in obesity with acute respiratory distress syndrome

BackgroundLimited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS.MethodsIn this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012–2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015–2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring.ResultsThe standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13–0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74).ConclusionIndividualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

When Less Is More: Why Extubation With Less Than Routine 100% Oxygen May Be a Reasonable Strategy.

When Less Is More: Why Extubation With Less Than Routine 100% Oxygen May Be a Reasonable Strategy.

Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants \u2013 study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy

BackgroundMost extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA.Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the hemoglobin oxygen saturation (SpO2) target range, number and duration of hypo- and hyperoxemic episodes and caregivers’ workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied.MethodsAn outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO2-C (in addition to routine manual control (RMC) of FiO2), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO2-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks).FiO2-C is provided by commercially available and CE-marked ventilators with an FiO2-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age.DiscussionShort-term studies on FiO2-C showed improved time ELGANs spent within their assigned SpO2 target range, but effects of FiO2-C on clinical outcomes are yet unknown and will be addressed in the FiO2-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO2-C may be implemented as standard therapy.Trial registrationThe study is registered at www.ClinicalTrials.gov: NCT03168516, May 30, 2017.

Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure.

Enhanced central chemoreflex (CC) gain is observed in volume overload heart failure (HF) and is correlated with autonomic dysfunction and breathing disorders. The aim of this study was to determine the role of the CC in the development of respiratory and autonomic dysfunction in HF. Volume overload was surgically created to induce HF in male Sprague-Dawley rats. Radiotelemetry transmitters were implanted for continuous monitoring of blood pressure and heart rate. After recovering from surgery, conscious unrestrained rats were exposed to episodic hypercapnic stimulation [EHS; 10 cycles/5 min, inspiratory fraction of carbon dioxide () 7%] in a whole body plethysmograph for recording of cardiorespiratory function. To determine the contribution of CC to cardiorespiratory variables, selective ablation of chemoreceptor neurons within the retrotrapezoid nucleus (RTN) was performed via injection of saporin toxin conjugated to substance P (SSP-SAP). Vehicle-treated rats (HF+Veh and Sham+Veh) were used as controls for SSP-SAP experiments. Sixty minutes post-EHS, minute ventilation was depressed in sham animals relative to HF animals (ΔV̇e: −5.55 ± 2.10 vs. 1.24 ± 1.35 mL/min 100 g, P < 0.05; Sham+Veh vs. HF+Veh). Furthermore, EHS resulted in autonomic imbalance, cardiorespiratory entrainment, and ventilatory disturbances in HF+Veh but not Sham+Veh rats, and these effects were significantly attenuated by SSP-SAP treatment. Also, the apnea-hypopnea index (AHI) was significantly lower in HF+SSP-SAP rats compared with HF+Veh rats (AHI: 5.5 ± 0.8 vs. 14.4 ± 1.3 events/h, HF+SSP-SAP vs. HF+Veh, respectively, P < 0.05). Finally, EHS-induced respiratory-cardiovascular coupling in HF rats depends on RTN chemoreceptor neurons because it was reduced by SSP-SAP treatment. Overall, EHS triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on RTN chemoreceptor neurons.

Can Hyperoxic Preconditioning in Normobaric Hypoxia (3500m) Improve All-Out Exercise Performance in Highly Skilled Skiers? A Randomized Crossover Study.

The altering effects of hypoxia on aerobic/anaerobic performance are well documented and form the basis of this study. Application of hyperoxic gases (inspiratory fraction of oxygen [FiO2] > 0.2095) prior to competition or training (hyperoxic preconditioning) can compensate for the negative influence of acute hypoxia. To investigate whether oxygen supplementation immediately prior to exercise (FiO2 = 1.0) improves all-out exercise performance in normobaric hypoxia (3500m) in highly skilled skiers. In this single-blind, randomized, crossover study, 17 subjects performed a 60-second constant-load, all-out test in a normobaric hypoxic chamber. After a short period of adaptation to hypoxia (60 min), they received either pure oxygen or chamber air for 5 minutes prior to the all-out test (hyperoxic preconditioning vs nonhyperoxic preconditioning). Capillary blood was collected 3 times, and muscle oxygenation was assessed with near-infrared spectroscopy. Absolute and relative peak power (P = .073 vs P = .103) as well as mean power (P = .330 vs P = .569) did not significantly differ after the hyperoxic preconditioning phase. PaO2 increased from 51.3 (3) to 451.9 (89.0)mm Hg, and SaO2 increased from 88.2% (1.7%) to 100% (0.2%) and dropped to 83.8% (4.2%) after the all-out test. Deoxygenation (P = .700) and reoxygenation rates (P = .185) did not significantly differ for both preconditioned settings. Therefore, the authors conclude that hyperoxic preconditioning did not enhance 60-second all-out exercise performance in acute hypoxia (3500m).

The Effect of Xenon-Based Anesthesia on Somatosensory-Evoked Potentials in Patients Undergoing Carotid Endarterectomy

The aim of this study was to investigate the influence of xenon-based anesthesia on somatosensory-evoked potentials. Observational cohort study. University hospital. Twenty subsequent adult patients undergoing elective carotid endarterectomy. Xenon-based anesthesia. Cortical-evoked responses to median nerve stimulation were quantified by measurement of the amplitude and latency of the N20 wave, which are typically assessed during carotid surgery to detect intraoperative cerebral hypoperfusion and ischemia. Primary (N20 amplitude and latency) and secondary (mean arterial pressure, norepinephrine requirements and depth of anesthesia) were assessed during (1) propofol/remifentanil and (2) subsequent xenon/remifentanil anesthesia. Xenon at an inspiratory fraction of 62.5 ± 7% decreased norepinephrine requirement (0.067 ± 0.04 v 0.028 ± 0.02 µg/kg/min, p < 0.001), and mean arterial pressure was unchanged (90.6 ± 15.0 v 93.1 ± 9.6 mmHg, p = 0.40). Somatosensory-evoked potentials were available in all patients during xenon/remifentanil. Despite similar depth of anesthesia (Narcotrend index 38.4 ± 6.2 v 38.5 ± 5.8) during propofol and xenon, N20 amplitude was reduced after xenon wash-in from 3.7 ± 1.7 to 1.4 ± 2.8 µV, p < 0.001 on the surgical and 3.6 ± 1.6 to 1.4 ± 0.6 µV, p < 0.001 on the contralateral side. N20 latency remained unchanged during xenon (22.9 ± 2.1 v 22.5 ± 2.8 ms, p = 0.34 and 22.9 ± 2.0 v 22.9 ± 3.0, p = 0.97). Xenon influences somatosensory-evoked potentials measurement by reducing N20 wave amplitude but not latency. When xenon is considered as an anesthetic for carotid endarterectomy, wash-in needs to be completed before carotid surgery is commenced to provide stable baseline somatosensory-evoked potential measurement.

Impact of Hyperoxic Preconditioning in Normobaric Hypoxia (3500m) on Balance Ability in Highly Skilled Skiers: A Randomized, Crossover Study.

To investigate whether hyperoxic preconditioning (pure-oxygen supplementation prior to exercise) improves balance ability and postural stability during normobaric hypoxia (3500m) in highly skilled skiers. In this single-blind randomized, crossover study, 19 subjects performed a 60-s balance test (MFT S3-Check) in a normobaric hypoxic chamber. After a short period of adaptation to hypoxia (60min), they received either pure oxygen or chamber air for 5min prior to a balance test (hyperoxic preconditioning vs nonhyperoxic preconditioning). Capillary blood was collected 3 times. Balance performance, indexed by sensory (P = .097), stability (P = .937), and symmetry (P = .202) scores, was not significantly different after the hyperoxic preconditioning phase. Balance performance decreased over time (no group difference). After hyperoxic preconditioning, arterial partial pressure of oxygen increased from 52.7 (4.5)mm Hg to 212.5 (75.8)mm Hg, and oxygen saturation of hemoglobin increased from 85.8% (3.5%) to 98.9% (0.7%) and remained significantly elevated to 90.1% (2.0%) after the balance test. A hyperoxic preconditioning phase does not affect balance performance under hypoxic environmental conditions. A performance-enhancing effect, at least in terms of coordinative functions, was not supported by this study.

Area under the forced expiratory flow-volume loop in spirometry indicates severe hyperinflation in COPD patients.

BackgroundSevere hyperinflation causes detrimental effects such as dyspnea and reduced exercise capacity and is an independent predictor of mortality in COPD patients. Static lung volumes are required to diagnose severe hyperinflation, which are not always accessible in primary care. Several studies have shown that the area under the forced expiratory flow-volume loop (AreaFE) is highly sensitive to bronchodilator response and is correlated with residual volume/total lung capacity (RV/TLC), a common index of air trapping. In this study, we investigate the role of AreaFE% (AreaFE expressed as a percentage of reference value) and conventional spirometry parameters in indicating severe hyperinflation.Materials and methodsWe used a cohort of 215 individuals with COPD. The presence of severe hyperinflation was defined as elevated air trapping (RV/TLC >60%) or reduced inspiratory fraction (inspiratory capacity [IC]/TLC <25%) measured using body plethysmography. AreaFE% was calculated by integrating the maximal expiratory flow-volume loop with the trapezoidal rule and expressing it as a percentage of the reference value estimated using predicted values of FVC, peak expiratory flow and forced expiratory flow at 25%, 50% and 75% of FVC. Receiver operating characteristics (ROC) curve analysis was used to identify cut-offs that were used to indicate severe hyperinflation, which were then validated in a separate group of 104 COPD subjects.ResultsROC analysis identified cut-offs of 15% and 20% for AreaFE% in indicating RV/TLC >60% and IC/TLC <25%, respectively (N=215). On validation (N=104), these cut-offs consistently registered the highest accuracy (80% each), sensitivity (68% and 75%) and specificity (83% and 80%) among conventional parameters in both criteria of severe hyperinflation.ConclusionAreaFE% consistently provides a superior estimation of severe hyperinflation using different indices, and may provide a convenient way to refer COPD patients for body plethysmography to address static lung volumes.

High-flow nasal cannula oxygen therapy decreases postextubation neuroventilatory drive and work of breathing in patients with chronic obstructive pulmonary disease

BackgroundThe physiological effects of high-flow nasal cannula O2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure. In this study, we compared the effects of HFNC and conventional low-flow O2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure.MethodsThis was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies. After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O2 therapy via a face mask. The inspiratory fraction of oxygen was titrated to achieve an arterial O2 saturation target of 88–92%. Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTPDI/min)) were recorded.ResultsEAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 μV switching from HFNC1 to conventional O2, and then returned to 15.2 ± 6.4 μV during HFNC2 (conventional O2: p < 0.05 versus HFNC1 and HFNC2). Similarly, the PTPDI/min increased from 135 ± 60 to 211 ± 70 cmH2O/s/min, and then decreased again during HFNC2 to 132 ± 56 (conventional O2: p < 0.05 versus HFNC1 and HFNC2).ConclusionsIn patients with COPD, the application of HFNC postextubation significantly decreased the neuroventilatory drive and work of breathing compared with conventional O2 therapy.

Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants

ObjectiveTo determine the association between SpO2 at 5 min and preterm infant outcomes.DesignData from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (≤0.3) versus higher...

Patterns of Oxygen Pulse Curve in Response to Incremental Exercise in Patients with Chronic Obstructive Pulmonary Disease \u2013 An Observational Study

In COPD, pulmonary hyperinflation causes decreased stroke volume thereby decreased oxygen pulse (O2P). While O2P flattening is related to myocardial ischemia in cardiac patients, O2P patterns have seldom been explored in COPD. The aims of the study were to investigate O2P-curve patterns and associated factors in COPD. Seventy-five patients with stable COPD were enrolled. The demographics, cardiac size, physiological measurements and stress EKG were compared among O2P-curve pattern groups. An algorithm to identify O2P-curve patterns was developed in 28 patients. In the remaining 45 patients after excluding two with poor effort, this algorithm revealed 20 (44%) flattening, 16 (36%) increasing, and nine (20%) decreasing patterns. The flattening-type group had lower body mass, cardiac size, and diffusing capacity, and larger lung volumes (p = 0.05–<0.0001) compared to the increasing-type group. During exercise, the flattening-type group had a lower operable O2P and more hyperventilation and dyspnea (p = 0.02–<0.01). None had ST-T changes. Most differences were related to body mass and mildly to inspiratory fraction. The decreasing-type group performed higher effort than the increasing-type group (p < 0.05). In conclusion, O2P flattening was common and was associated with reduced body mass and pulmonary hyperinflation rather than with myocardial ischemia. The decreasing-type may be caused by motivation to exercise.

A case of unexpected impaired oxygenation due to intraoperative pneumothorax: an adverse event associated with respiratory management with spontaneous respiration in a patient with esophagobronchial fistulae

BackgroundRespiratory management in patients with esophagobronchial fistulae is challenging since positive pressure ventilation (PPV) may not be feasible due to air leaks and possible risks for regurgitation and aspiration of gastric contents. We and others have previously reported that spontaneous respiration may be one of the good options of respiratory management during general anesthesia in those patients. However, adverse events associated with this respiratory strategy have not been reported previously. We experienced a 77-year-old male patient who suffered unexpected impairment of oxygenation due to intraoperative pneumothorax, which was assumed to have been exacerbated by spontaneous respiration during esophageal bypass surgery.Case presentationThe patient was planned to undergo esophageal bypass surgery for esophagobronchial fistulae associated with malignant esophageal cancer. Both of two esophagobronchial fistulae were located in the proximal part of the left main bronchus. For the risks of air leaks and aspiration associated with PPV and further damage to the tissue around the fistulae, we decided to maintain spontaneous respiration under general anesthesia and obtain abdominal muscle relaxation with epidural anesthesia. After catheterization of epidural anesthesia, the patient was sedated with 35 mg of intravenous pethidine and was nasotracheally intubated under bronchoscopic guidance. We confirmed that the tip of the tracheal tube was located above the carina. Then anesthesia was induced and maintained with sevoflurane so that his spontaneous respiration could be maintained thereafter. His spontaneous respiration was assisted with 3 cmH2O of pressure support. Approximately 60 min into the surgery, percutaneous arterial oxygen saturation (SpO2) suddenly dropped from 99 to 89% with an inspiratory fraction of oxygen of 0.4. We assumed that lung atelectasis associated with airway secretion or pulmonary soiling was the most likely reason for impaired oxygenation; however, arterial oxygenation only partially regained even after they were suctioned. After the completion of the surgery, chest X-ray revealed right pneumothorax. After a chest drainage tube was inserted, right pneumothorax was ameliorated and SpO2 returned to the baseline level.ConclusionsAlthough spontaneous respiration may be useful in a patient with esophagobronchial fistulae, oxygenation can be impaired more seriously than PPV in case intraoperative pneumothorax occurs.

A Possible Case of Neurogenic Pulmonary Edema in a Sheep following Intracranial Surgery

Abstract Objective: To describe presentation, treatment and outcome of a sheep that developed acute respiratory distress after intracranial surgery. Case summary: A 3-year-old female crossbred sheep weighing 64 kg was anaesthetized for intracranial surgery as a part of a research project. Premedication and induction of anesthesia were uneventful as well as tracheal intubation. Anesthesia was maintained with isoflurane in a 50% mixture of oxygen and air, fentanyl (5-15 μg kg-1h-1) and lidocaine (1.8 mg kg-1h-1). During anesthesia, an increased alveolar-arterial oxygen gradient was calculated on the basis of arterial blood gas analysis: inspiratory fraction of oxygen was increased and a recruitment manoeuvre was performed. After 210 minutes of anesthesia, the sheep was let recover with oxygen supplementation under monitoring of pulse-oxymetry, capnography, inspired and expired oxygen, temperature and invasive blood pressure. At tracheal extubation no signs of regurgitation or aspiration were noticed. Twenty-five minutes later, the sheep showed deterioration of neurological status and clonic seizure responsive to diazepam. After transient tachycardia, blood pressure rose acutely and sinus bradycardia followed. Severe tachypnea started in few minutes accompanied by loud respiratory noises and harsh diffuse crackles on both sides of the thorax. Foamy blood nasal exudates discharged from the nostrils. Neurogenic pulmonary edema as a sequel of increased intracranial pressure was suspected and treated with intravenous mannitol (0.5 gkg-1) and furosemide (4 mgKg-1). Hypoxemia was successfully managed with oxygen supplementation. Motor and cognitive functions improved progressively and were deemed normal within 12 hours from the episode, when arterial partial pressure of oxygen was 11.7 kPa (88 mmHg) at room air. New information provided: Severe pulmonary complications may be observed after iatrogenic neurological injury in sheep. Neurogenic pulmonary edema should be taken into account among the differential diagnoses of abrupt respiratory distress following seizure.

Survival and Neurodevelopmental Outcomes of Preterms Resuscitated With Different Oxygen Fractions.

Stabilization of preterm infants after birth frequently requires oxygen supplementation. At present the optimal initial oxygen inspiratory fraction (Fio2) for preterm stabilization after birth is still under debate. We aimed to compare neurodevelopmental outcomes of extremely preterm infants at 24 months corrected age randomly assigned to be stabilized after birth with an initial Fio2 of 0.3 versus 0.6 to 0.65 in 3 academic centers from Spain and the Netherlands. Randomized, controlled, double-blinded, multicenter, international clinical trial enrolling preterm infants <32 weeks' gestation assigned to an initial Fio2 of 0.3 (Lowox group) or 0.6 to 0.65 (Hiox group). During stabilization, arterial pulse oxygen saturation and heart rate were continuously monitored and Fio2 was individually titrated to keep infants within recommended ranges. At 24 months, blinded researchers used the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) to assess visual acuity, neurosensory deafness, and language skills. A total of 253 infants were recruited and 206 (81.4%) completed follow-up. No differences in perinatal characteristics, oxidative stress, or morbidities during the neonatal period were assessed. Mortality at hospital discharge or when follow-up was completed didn't show differences between the groups. No differences regarding Bayley-III scale scores (motor, cognitive, and language composites), neurosensorial handicaps, cerebral palsy, or language skills between groups were found. The use of an initial lower (0.3) or higher (0.6-0.65) Fio2 during stabilization of extremely preterm infants in the delivery room does not influence survival or neurodevelopmental outcomes at 24 months.

Control theory prediction of resolved Cheyne-Stokes respiration in heart failure.

Cheyne-Stokes respiration (CSR) foretells deleterious outcomes in patients with heart failure. Currently, the size of therapeutic intervention is not guided by the patient's underlying pathophysiology. In theory, the intervention needed to resolve CSR, as a control system instability (loop gain >1), can be predicted knowing the baseline loop gain and how much it falls with therapy.In 12 patients with heart failure, we administered an inspiratory carbon dioxide fraction of 1-3% during CSR (n=95 interventions) as a means to reduce loop gain. We estimated the loop gain on therapy (LGtherapy), using the baseline loop gain (using hyperpnoea length/cycle length) and its expected reduction (18% per 1% inspired carbon dioxide), and tested the specific hypothesis that LGtherapy predicts CSR persistence (LGtherapy >1) versus resolution (LGtherapy <1).As predicted, when LGtherapy >1.0, CSR continued during therapy in 23 out of 25 (92%) trials. A borderline loop gain zone (0.8<LGtherapy<1) yielded an unpredictable outcome, while LGtherapy <0.8 consistently yielded CSR resolution (37 out of 37 trials). A threshold of LGtherapy=0.9 determined outcome in 76 out of 95 (80%) trials.We establish proof-of-concept that control theory provides predictive insight into CSR resolution in heart failure. Thus, we now have a means to calculate the size of interventions needed to ameliorate CSR on a patient-by-patient basis.

Inspiratory fraction as a marker of skeletal muscle dysfunction in patients with COPD

BackgroundAn inspiratory capacity to total lung capacity (IC/TLC) ratio of ≤25% has emerged as a better marker of mortality in chronic obstructive pulmonary disease (COPD) patients. The relationship among the IC/TLC ratio to lower extremity skeletal muscle function remains unknown. MethodsThirty-five men with moderate to severe COPD were divided into those with IC/TLC≤25% (n=16) and >25% (n=19). The subjects were tested for thigh muscle mass volume (MMT), maximal strength, power output of the lower extremities, and physical activity. ResultsTotal MMT in the IC/TLC<25% group was significantly lower (413.91±89.42cm3) (p<0.001) than in the IC/TLC>25% group (575.20±11.76cm3). In the IC/TLC≤25% group, maximal strength of the lower extremities and muscle peak power output of the lower extremities were 36–56% lower (p<0.01) than among the patients in the IC/TLC>25% group. ConclusionIC/TLC≤25% is associated with reduced maximal strength and peak power output of the lower extremities. IC/TLC≤25% may have an important clinical relevance as an index to determine peripheral muscle dysfunction.

Chronic phenytoin treatment reduces rat carotid body chemosensory responses to acute hypoxia

Ventilation is peripherally controlled by afferent activity arising from the peripheral chemoreceptors. In the rat, chemosensory activity is conveyed to the central nervous system through axons of neurons located in the nodose-petrosal-jugular-complex. These neurons have distinct electrophysiological properties, including a persistent Na+ current. Acute blockade of this current with phenytoin and other anti-epileptic drugs reduces normoxic chemosensory activity and responses to acute hypoxia. However, because anti-epileptic therapy is prolonged and there is no information on the effects of chronic phenytoin treatment on peripheral chemosensory activity, we studied the effects of long-lasting phenytoin treatment (~25 days) on afferent chemosensory activity, on a wide range of oxygen inspiratory fractions. Osmotic pumps containing dissolved phenytoin (166mg/mL) or vehicle (daily flow: 60µL) were implanted subcutaneously in male adult Sprague Dawley rats. At the end of the treatment, the animals were anesthetized and carotid sinus nerve activity was recorded in vivo. Afferent chemosensory activity in normoxia was not significantly different between control (71.2±2.2Hz) and phenytoin treated (95.4±2.1Hz) rats. In contrast, carotid body chemosensory responses to acute hypoxic challenges were markedly reduced in phenytoin treated rats, specifically in the lowest part of the hypoxic range (control 133.5±18.0Hz vs phenytoin treated 50.2±29.4, at 5% FIO2). Chronic phenytoin treatment severely impaired the chemosensory responses to acute hypoxia, suggesting that long-term phenytoin treatment in patients may result in a reduced peripheral respiratory drive together with a reduction in the respiratory responses to hypoxic challenges.