Supplemental O2 Research Articles

Caffeine versus aminophylline in combination with oxygen therapy for apnea of prematurity: A retrospective cohort study.

The present study was conducted to investigate the clinical significance of caffeine and aminophylline in the treatment of premature infants with apnea under varying conditions of oxygen (O2) delivery. The clinical data of 120 premature infants with apnea treated with oxygen therapy and either caffeine citrate (20 mg/kg/day; n=77) or aminophylline (10 mg/kg/day; n=43) were retrospectively examined. The therapeutic performance of the drugs after the completion of the treatment was evaluated primarily according to the risk of recurrent episodes of apnea, the changes in the duration and concentration of inhaled O2 and the incidence of complications. In contrast to aminophylline, caffeine treatment significantly reduced the duration of O2 inhalation and the inhaled O2 concentration in the infants treated with mechanical ventilation or O2 delivery devices (P<0.05). Treatment with caffeine also decreased the incidence of recurrent apnea events and complications in the investigated population (P<0.05 or P<0.01). Caffeine performs better than aminophylline in the treatment of premature infants with apnea under different conditions of O2 delivery. The therapeutic performance of caffeine is achieved primarily via improving the efficacy of supplemental O2 and reducing the incidence of complications.

Abstract CT403: Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments

Abstract Background: The SARS-CoV-2 outbreak in Paris’ region significantly affected Gustave Roussy cancer center. Here, we report the Gustave Roussy experience during the SARS-CoV-2 outbreak. This outbreak has led to a rapid reorganization of cancer patients’ (pts) management, with two concurrent objectives. First, protect cancer pts, who may experience more severe form of the disease, from being infected by the SARS-CoV-2. Second, protect cancer pts from losing the chance to receive optimal, if not standard, cancer care. Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March, 12th. Screening indications have been adapted over the time. All the COVID19 pts positively tested and managed at Gustave Roussy between March 14th (1st positive case) and April 15th have been included in a redcap database. Pts and underlying oncological and COVID19 diseases characteristics have been collected. Cancer and COVID-19 managements, and outcomes have been assessed. The primary endpoint of this analysis was the clinical deterioration, defined as the need for O2 supplementation of 6l/min or more, or death of any cause. Results: Overall, 7,251 cancer pts were managed at Gustave Roussy during this period of time, with 3616 being hospitalized. Based on our testing strategy, 1302 pts have been tested with 12% of them found positive for SARS-CoV-2. Among the first 137 cancer pts diagnosed with SARS-CoV-2, most cases were female (58%) with a median age of 61 years, including 36 pts (26%) ≥ 70 years. Most frequent underlying cancers were solid tumors (115) including breast (23), GI (18), head and neck (17), GU (17), GYN (17) malignancies or hemopathies (22). At time of COVID diagnosis, 79 pts (58%) had metastatic/active cancer and 56 pts (41%) were considered in remission/treated with curative intent. The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 93.4% and 6.6% of the cases, respectively. The majority of the pts was hospitalized (75%) and treated with HCQ/AZI (40; 30%) with inclusion in the ONCOVID trial (EudraCT: 2020-01250-21), IL-6 inhibitor (10), antiviral (6) or steroids (13). Fifteen pts were admitted in ICU (11%). Clinical deterioration occurred in 34 pts (24.8%) and was associated with hematological underlying disease, CRP at diagnosis of COVID19 &amp;gt;50 and the use of cytotoxic chemotherapy within &amp;lt;3mo. At data cut-off (April, 20th 2020), 95 (69.3%), 20 (14.6%), and 22 (16.1%) pts were discharged, had died, or were still hospitalized, respectively. All the deaths were considered related to the SARS-CoV-2 infection. Conclusions: Globally, the rate of the SARS-CoV-2 infection in our cancer patients’ population does not seem to be higher compared to the global population. We have not found evidence that COVID19 is more lethal or aggressive in cancer patients that underwent usual SARS-Cov-2 treatment. We believe that adequate testing and protective measures, along with the low rate of SARS-cov-2-treatment-related adverse events (5.5%), justify an optimal management of the cancer patients’ underlying tumor. Citation Format: Fabrice Barlesi, Stéphanie Foulon, Arnauld Bayle, Bertrand Gachot, Fanny Pommeret, Christophe Willekens, Annabelle Stoclin, Mansouria Merad, Franck GriscelliI, Jean-Baptise Micol, Roger Sun, Thomas Nihouarn, Corinne Balleygier, Fabrice André, Florian Scotte, Benjamin Besse, Jean-Charles Soria, Laurence Albiges. Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT403.

Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle.

Preterm infants can develop airway hyperreactivity and impaired bronchodilation following supplemental O2 (hyperoxia) in early life, making it important to understand mechanisms of hyperoxia effects. Endogenous hydrogen sulfide (H2 S) has anti-inflammatory and vasodilatory effects with oxidative stress. There is little understanding of H2 S signaling in developing airways. We hypothesized that the endogenous H2 S system is detrimentally influenced by O2 and conversely H2 S signaling pathways can be leveraged to attenuate deleterious effects of O2 . Using human fetal airway smooth muscle (fASM) cells, we investigated baseline expression of endogenous H2 S machinery, and effects of exogenous H2 S donors NaHS and GYY4137 in the context of moderate hyperoxia, with intracellular calcium regulation as a readout of contractility. Biochemical pathways for endogenous H2 S generation and catabolism are present in fASM, and are differentially sensitive to O2 toward overall reduction in H2 S levels. H2 S donors have downstream effects of reducing [Ca2+ ]i responses to bronchoconstrictor agonist via blunted plasma membrane Ca2+ influx: effects blocked by O2 . However, such detrimental O2 effects are targetable by exogenous H2 S donors such as NaHS and GYY4137. These data provide novel information regarding the potential for H2 S to act as a bronchodilator in developing airways in the context of oxygen exposure.

Utility of polysomnography and video swallow studies in the management of pediatric patients with congenital idiopathic bilateral vocal fold dysfunction

ObjectivesCongenital idiopathic bilateral vocal fold dysfunction (BVFD) is an uncommon cause of neonatal stridor and respiratory distress postnatally. Approximately 50% of affected neonates or infants will historically require tracheostomy for this condition. Timing and candidacy for tracheostomy in BVFD patients is often subjective and poorly understood. Polysomnography (PSG) and video swallow studies (VSS) may be helpful in the management of patients with BVFD prior to tracheostomy by quantifying their degree of upper airway obstruction during sleep and feeding dysfunction while awake. MethodsWe performed a single-institution retrospective case series of BVFD patients from 2000 to 2018 who had postnatal PSGs performed prior to tracheostomy. Demographics, gestational age, and VSS results prior to PSG were recorded for all patients. Findings from PSGs included non-REM AHI, REM AHI, oxygen nadir, % total sleep time (TST) O2<90%, peak end-tidal (ET) CO2, % TST ETCO2 >52 torr. Rates of post-PSG tracheostomy, gastrostomy tube (G-tube) placement, and home O2 supplementation were noted for all patients. ResultsFrom 2000 to 2018, 12/46 (26%) BVFD patients had postnatal PSGs performed prior to tracheostomy. Median patient age at BVFD diagnosis, VSS, and PSG was 5.5 days, 12.5 days, and 17.5 days, respectively. Mild, moderate, and severe obstructive sleep apnea (OSA) was found in 7/12, 3/12, and 4/12 patients, respectively. Hypercapnia (ETCO2 >52 torr) was found in 5/12 patients on PSG while hypoxemia (SpO2 <90% for >4% TST) was not found in any patient. VSS results demonstrated normal swallowing, inconsistent laryngeal penetration, and silent aspiration in 7/12, 2/12, and 3/12 patients, respectively. Tracheostomy and G-tube placement was performed in 3/12 and 2/12 patients, respectively. There was no association between the severity of OSA or any PSG abnormality, VSS findings, and the performance of tracheostomy in any BVFD patient. ConclusionsOSA was found in all BVFD patients undergoing postnatal PSG at our institution while feeding dysfunction was found in approximately 50% of patients. The presence of feeding dysfunction, severe OSA, or any PSG abnormality was not individually associated with the subsequent performance of a tracheostomy in our patients. PSG is likely useful in supporting but not supplanting one's clinical decision-making in the management of patients with congenital idiopathic BVFD.

Perimortem Cesarean Section : As Resucitative Hysterotomy On Maternal Cardiac Arrest

Maternal cardiac arrest or maternal collaps is defined as an acute event involving the cardiorespiratory systems and/or brain, resulting in a reduced or absent consciousness level (and potentially death), at any stage in pregnancy and up to six weeks after delivery. Perimortem Cesarean Section (PCS) is performed either during maternal cardiac arrest or during impending maternal cardiac arrest toresuscitate mother and fetal. Current recommendations for maternal resuscitation include performance of the procedure following five minutes of unsuccessful cardiopulmonary resuscitation. The most common aetiology of maternal collaps was know as “4 H and 4 T” (Hypovolemia, Hypoxia, Hypo/Hyperkalemia,Hypothermia; Tromboembolism, Toxicity, Tension pneumothorax, Tamponade). Resuscitation in maternal cardiac arrest is mostly similar with non-pregnant patient resuscitation. There are several considerations need to be addressed in primary survey such as endotracheal tube 1 size smaller, supplemental O2 regardless of peripheral saturation, aggressive volume resuscitation, and uterine displacement to relieve compression of the IVC.Keywords: Maternal cardiac arrest; non-pregnant patient resuscitation

Perimortem Cesarean Section : As Resucitative Hysterotomy On Maternal Cardiac Arrest

Maternal cardiac arrest or maternal collaps is defined as an acute event involving the cardiorespiratory systems and/or brain, resulting in a reduced or absent consciousness level (and potentially death), at any stage in pregnancy and up to six weeks after delivery. Perimortem Cesarean Section (PCS) is performed either during maternal cardiac arrest or during impending maternal cardiac arrest toresuscitate mother and fetal. Current recommendations for maternal resuscitation include performance of the procedure following five minutes of unsuccessful cardiopulmonary resuscitation. The most common aetiology of maternal collaps was know as “4 H and 4 T” (Hypovolemia, Hypoxia, Hypo/Hyperkalemia,Hypothermia; Tromboembolism, Toxicity, Tension pneumothorax, Tamponade). Resuscitation in maternal cardiac arrest is mostly similar with non-pregnant patient resuscitation. There are several considerations need to be addressed in primary survey such as endotracheal tube 1 size smaller, supplemental O2 regardless of peripheral saturation, aggressive volume resuscitation, and uterine displacement to relieve compression of the IVC.Keywords: Maternal cardiac arrest; non-pregnant patient resuscitation

Pulse Oximetry is Essential in Home Management of Elderly COVID-19 Patients

Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) is in Pandemic form and has affected people of 215 countries. It produces symptoms like fever, cough, shortness of breath, sore throat, headache, loss of taste, smell or appetite and many other rare symptoms. But the most important symptom is shortness of breath due to hypoxia. In a normal individual oxygen saturation (SpO2) is at least 95% and patient feels shortness of breath when SpO2 falls below 90% with some exception. SARS-CoV-2, a newly emergent coronavirus has the peculiarity to produce silent hypoxia, meaning SpO2&lt; 90% or less like 80%, 70%, 60% without shortness of breath. Silent hypoxia can be diagnosed by monitoring SpO2 with pulse oximeter. For management of COVID-19, early symptoms like fever &amp; cough, SpO2 should be monitored by pulse oximeter, followed by immediate correction of hypoxia by O2 supplementation and prophylactic oral or injectable anticoagulant to prevent thromboembolism and thus death rate can be reduced. Case summary: A 72-year-old man presented with the complaints of fever and headache followed by cough, fatigue, anorexia, loss of taste and appetite in next few days but no shortness of breath. The patient was clinically diagnosed as a case of COVID-19 &amp; positive result of Real time-Polymerase Chain Reaction (RT-PCR) test confirmed the diagnosis. From the first day, SpO2 was regularly monitored with pulse oximeter and SpO2 on day 1, it was 96-98%. On day 8, SpO2 fell to 89-93%, pulse 96/min, respiratory rate&gt;30/min, temperature 101° F, taste sensation was reduced. According to sign and symptoms, the patient was diagnosed as COVID-19 with severe pneumonia. Management was started at home with continuous monitoring, lying in prone position for 5-6 hours/day, supplemental oxygenation to maintain level of SpO2 between 94-96%, injectable anticoagulant enoxaparin to prevent venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) was given. Prophylactic antibiotics and symptomatic treatment were also given. Results: According to this case report, patient’s SpO2 was monitored by pulse oximeter on first day; on day 08, SpO2 fell to 89-93% &amp; on day 10, further dropped to 85-88% which indicated severe pneumonia but there was no complaint of breathlessness as it was silent hypoxia. Sometimes the patient spent 30 minutes or more in toilet and SpO2 used to fall to 82-83% without any subjective shortness of breath but with only mild heaviness of chest and cough. Therefore SpO2 monitoring by pulse oximeter is essential in early diagnosis of silent hypoxia. Correction of hypoxia by supplemental oxygenation and prevention of VTE and DIC by using anticoagulant was the mainstay of treatment and patient had significant improvement on day 14. The patient was managed completely at home except X-ray being done in a hospital. Conclusion: Fall of SpO2 in COVID-19 i.e. hypoxia (usually present as shortness of breath) or silent hypoxia can be diagnosed early by pulse oximeter or smart phone pulse oximetry apps. Early management by isolation, supplemental oxygenation and oral/injectable anticoagulation can prevent further events like Acute Respiratory Distress Syndrome (ARDS), respiratory failure followed by multiple organ failure (that may cause death). The authors advocate further clinical trial and research. Bangladesh J Otorhinolaryngol; April 2020; 26(1): 55-67

Approaching COVID-19-Bedside strategies for intensive care.

The spread of novel coronavirus disease (COVID‐19) urged a never‐seen coordinated global response to prepare the health system, including primary care, hospital facilities and intensive care units (ICUs). Lessons have been learned from countries who suffered the pandemic at the beginning, helping the ones which are on different phases of the spreading curve. Currently, optimizing intensive care resources is mandatory as admittance to the ICUs remains rising exponentially. While public and private health system struggle for changing the slope of the curve, intensivists prepare the facilities for a tsunami of respiratory failure patients with COVID‐19.1

Oxyhemoglobin desaturation as a function of age and hypercapnia from ventilatory pump failure (VPF)

Background:Supplemental O2 is often administered without knowledge of CO2 levels for patients with ventilatory pump failure (VPF). This can render oximetry ineffective as a gauge of alveolar ventilation, airway secretions, and lung disease. We have noted that diurnal hypoventilation with hypercapnia tends to be symptomatic when O2 saturation levels decrease below 95% and patients extend sleep noninvasive ventilatory support (NVS) into daytime hours. We also noted that with advancing age, less hypercapnia results in desaturation. This study was designed to explore oxyhemoglobin desaturations (O2 desats) as a function of age and hypercapnia for patients with VPF.Methods:A retrospective analysis of 8933 consecutive patient visits for whom end-tidal CO2 and O2 sats were measured. O2 sats &lt; 95% at CO2 levels of 45, 50, and 60 cmH2O were correlated with 10 years age intervals to age 80.Results:Of 8933 visits, 8642 had complete data. Outcomes for CO2 levels &gt; 50 cmH2O were the most significant including for visit-ages &lt; 30 and ≥ 30 years. There was a statistically significant 4% decrease in the odds of O2 desat for every one-year increase in age to age 30 (OR = 0.96, 95% CI = [0.93, 0.99], p = 0.02) and for visit-ages ≥ 30 a significant 30% increase in the odds of O2 desat for every 10-year increase in age (OR 1.3, 95% CI = [1.1, 1.6], p = 0.006). Relationship for ages ≥ 30 years were also significant for CO2 levels over 45 mmHg also. 40% of the time when CO2 was greater than 45 mmHg O2 sat was low.Discussion:This study demonstrated a significantly lower risk of O2 desat occurring at EtCO2 levels ≥ 50 mmHg for patients from 10 to 20 years of age than those younger than 10 and a significantly greater risk of O2 desat for 10 years intervals after age 20. Thus, with age, less hypercapnia results in desats and dyspnea with patients tending to extend NVS into daytime hours. This may be due to increases in physiological shunting, decreased pulmonary elasticity, and worsening ventilation/perfusion ratios with age.

The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content

Maternal oxygen (O2) administration is a commonly performed intrauterine resuscitation technique though to improve fetal oxygenation. However, hyperoxygenation is known to be harmful in both neonates and adults. Currently, there are no formal recommendations on whether a certain dose or duration of O2 may be most helpful in improving umbilical cord gases or neonatal outcomes. We tested the hypothesis that prolonged supplemental O2 exposure during labor is associated with increased umbilical cord O2 concentrations. This was a planned secondary analysis of a randomized noninferiority trial comparing O2 with room air in laboring patients. Patients were randomized to receive either 10 L/min O2 or room air at any point during active labor when they developed a category II fetal heart tracing that would otherwise require resuscitation. The primary outcome variable for this analysis was partial pressure of O2 in the umbilical vein. The secondary outcome variable was partial pressure of O2 in the umbilical artery. These outcome variables were compared between patients with short durations of O2 exposure and those with long durations of O2 exposure, defined as <75th percentile and ≥75th percentile of duration, respectively. The outcomes were also compared among the groups that received room air, O2 for short durations, and O2 for long durations. Among the 99 patients with paired and validated cord gases who were included in this analysis, the partial pressure of O2 in the umbilical vein was significantly lower in patients who received O2 supplementation for longer durations than in those who received O2 for shorter durations (median interquartile range 25.5 [21.5-33] vs 32.5 [26.5-37.5] mm Hg; P<.03). There was no difference in the partial pressure of O2 in the umbilical artery or other cord gases between the short and long duration O2 supplementation groups. Other methods of intrauterine resuscitation were similar between the short and long duration O2 supplementation groups. There was no difference in the partial pressure of O2 in the umbilical artery or in the umbilical vein when the room air, short duration O2 supplementation, and long duration O2 supplementation groups were compared. Longer durations of O2 exposure are not associated with a higher partial pressure of O2 in the umbilical cord. In fact, patients with longer durations of O2 exposure had lower partial pressure of O2 in the umbilical vein, suggesting impaired placental O2 transfer with prolonged O2 exposure.

Blood and urine biomarkers associated with long-term respiratory dysfunction following neonatal hyperoxia exposure: Implications for prematurity and risk of SIDS

Former preterm infants, many of whom required supplemental O2 support, exhibit sleep disordered breathing and attenuated ventilatory responses to acute hypoxia (HVR) beyond their NICU stay. There is an increasing awareness that early detection of biomarkers in biological fluids may be useful predictors/identifiers of short- and long-term morbidities. In the present study, we identified serotonin (5-HT), dopamine (DA) and hyaluronan (HA) as three potential biomarkers that may be increased by neonatal hyperoxia and tested whether they would be associated with an impaired HVR in a rat model of supplemental O2 exposure. Neonatal rats (postnatal age (P) 6 days, P6) exposed to hyperoxia (40% FIO2, 24 h/day between P1–P5 days of age) exhibited an attenuated early (1 min), but not the late (4−5 min) phase of the HVR compared to normoxia control rats; the attenuated early phase HVR was associated with increased levels of DA (urine and serum), 5-HT (platelet poor plasma only, PPP), and HA (serum only). At P21, both the early and late phases of the HVR were attenuated, but serum and urine levels of all 3 biomarkers were similar to age-matched control rats. These data indicate that changes in several serum and/or urine biomarkers (5-HT, DA, and HA) following short-term (days) neonatal hyperoxia can signify long-term (weeks) respiratory control dysfunction. Further studies are needed to determine whether early detection of similar biomarkers could be convenient predictors of increased risk of abnormalities in respiratory control including sleep disordered breathing in former preterm infants who had received prior supplemental O2 and who might also be at increased risk of SIDS.

MON-LB127 Pulmonary Embolism in the Setting of Diabetic Ketoacidosis. an Under-Recognized Complication

The relation between Diabetic Ketoacidosis and Venous Thromboembolism is important to appreciate for early recognition and management. 90 year old female with Type 2 DM was brought to the ER after a syncopal episode. Family reported the patient to be lethargic with a decreased appetite for one week. On arrival, patient had a blood pressure of 84/44 mmHg. Oxygen saturation was 89% at room air and improved to 93% on supplemental O2. Patient was afebrile with a respiratory rate of 16 and heart rate 89/minute. On exam, she was dehydrated with decreased skin turgor, dry oral mucosa. Labs revealed blood glucose of 621 mg/dL, Bicarbonate 16 mmol/L, B-Hydroxybutyrate 5.00 mmol/L, Anion Gap 21, pH of 7.26 on ABG. Urinalysis was suggestive of a urinary tract infection. After initiation of IV antibiotics and insulin, she was transferred to the intensive care unit. In the ICU, her blood pressure failed to improve with fluid resuscitation, ultimately requiring vasopressors. Due to hypotension with hypoxia, CT Chest was performed which revealed extensive bilateral PE. She was started on IV heparin infusion. Pro-Brain Natriuretic Peptide was elevated at 4,716 pg/mL. Echocardiogram confirmed right heart strain with severely dilated right ventricle, positive McConnell’s sign, systolic and diastolic septal flattening and an estimated RSVP 67mmHg consistent with moderately severe pulmonary hypertension. Tissue plasminogen activator was recommended however given the patient’s age and functional status; family decided against systemic thrombolysis. Duplex ultrasound of her lower extremities also showed bilateral acute deep venous thrombosis. She was continued on intravenous anticoagulation and eventually was able to come off vasopressors. As the patient’s blood glucose levels improved and her anion gap closed, she was transitioned to basal/bolus insulin and transferred to the general medical floor. She was started on Apixaban and discharged home per family’s request after her code status was changed to DNR-Comfort Care Arrest.Pulmonary embolism is a serious venous thromboembolic event that is rarely reported in association with DKA. Proposed mechanisms include some of the same mechanisms implicated in arterial thrombosis, namely abnormalities in coagulation factors, increased platelet aggregation, impaired fibrinolysis and endothelial injury due to hypertonicity. Also, severe dehydration associated with DKA may contribute by virtue of increased red blood cell rigidity and increased blood viscosity establishing DKA as an underlying cause or contributing factor of pulmonary thromboembolism2.1 Langevin C et al Presumed paradoxical embolus in a patient with diabetic ketoacidosis Int J Gen Med 2015;8:297–301 2015 Sep 182 Scordi Bello I et al Fatal Pulmonary Thromboembolism in Patients with Diabetic Ketoacidosis A Seven-Case Series and Review of the Literature Acad Forensic Pathol 2016;6(2):198–205

High-intensity interval training accelerates oxygen uptake kinetics and improves exercise tolerance for individuals with cystic fibrosis

BackgroundExercise training provides benefits for individuals with cystic fibrosis; however, the optimal program is unclear. High-intensity interval training is safe and effective for improving ‘functional capacity’ in these individuals with peak rate of O2 uptake typically referenced. The ability to adjust submaximal rate of oxygen uptake (V̇O2 kinetics) might be more important for everyday function because maximal efforts are usually not undertaken. Moreover, the ability of high-intensity training to accelerate V̇O2 kinetics for individuals with cystic fibrosis could be enhanced with O2 supplementation during training.MethodsNine individuals with cystic fibrosis completed incremental cycling to limit of tolerance followed by 8 weeks of high-intensity interval cycling (2 sessions per week x ~ 45 min per session) either with (n = 5; O2+) or without (AMB) oxygen supplementation (100%). Each session involved work intervals at 70% of peak work rate followed by 60 s of recovery at 35%. For progression, duration of work intervals was increased according to participant tolerance.ResultsBoth groups experienced a significant increase in work-interval duration over the course of the intervention (O2+, 1736 ± 141 v. 700 ± 154 s; AMB, 1463 ± 598 v. 953 ± 253 s; P = 0.000); however, the increase experienced by O2+ was greater (P = 0.027). During low-intensity constant-work-rate cycling, the V̇O2 mean response time was shortened post compared to pre training (O2+, 34 ± 11 v. 44 ± 9 s; AMB, 39 ± 14 v. 45 ± 17 s; P = 0.000) while during high-intensity constant-work-rate cycling, time to exhaustion was increased (O2+, 1628 ± 163 v. 705 ± 133 s; AMB, 1073 ± 633 v. 690 ± 348 s; P = 0.002) and blood [lactate] response was decreased (O2+, 4.5 ± 0.9 v. 6.3 ± 1.4 mmol. L− 1; AMB, 4.5 ± 0.6 v. 5.2 ± 1.4 mmol. L− 1; P = 0.003). These positive adaptations were similar regardless of gas inspiration during training.ConclusionEight weeks of high-intensity interval training for patients with cystic fibrosis accelerated V̇O2 kinetics and increased time to exhaustion. This provides some evidence that these patients may benefit from this type of exercise.Trial registrationThis study was retrospectively registered in the ISRTCN registry on 22/06/2019 (#ISRCTN13864650).

Calcium‐Sensing Receptor (CaSR) Modulates Hyperoxia‐Induced Airway Hyperreactivity In a Neonatal Mouse Model of Bronchopulmonary Dysplasia

Supplemental O2 is a primary mode of respiratory therapy for preterm infants. Numerous studies, however, have shown that supplemental O2 may contribute to the pathophysiology of airway hyperreactivity (AHR) associated with wheezing disorders such as asthma later in childhood. The calcium‐sensitive receptor (CaSR) is a potent modulator of smooth muscle contractility and may be an underlying feature of childhood asthma. In the present study, we investigated whether CaSR is involved in neonatal hyperoxia induced AHR in a mouse model of BPD. We hypothesize that inhibition (CaSR antagonism), downregulation of expression (siRNA), or deletion (CaSR KO mice) of CaSR will attenuate the AHR induced by hyperoxia in neonatal mice. Newborn C57BL/6 wild‐type (background) or CaSR−/− (knockout) mice were randomized on the second day of life and assigned to room air (21% O2) or hyperoxic (40% O2) groups and exposed for seven days, then recovered in room air for two additional weeks. At day P21, AHR was assessed in vitro using precision‐cut living lung slice preparations in response to increasing doses of methacholine (MCh, 0.25–8 μM). Wild‐type lung slices were pre‐incubated for 48 h in a CaSR siRNA sequence (40 nM) or scrambled RNA as a negative control. In another set of experiments, slices were pre‐incubated in a CaSR antagonist – NPS 2143 (10 nM) for 1 h. Airways were imaged and airway reactivity was expressed as percent change from baseline airway lumen area (± SEM). Neonatal hyperoxia significantly increased airway contractile responses to MCh in wild‐type mice with a mean maximal effect (Emax) of 68.4±8.7% decrease in airway lumen area compared to room air controls (47.3±5.8%, p&lt;0.001), indicating AHR. Pre‐incubation (48hrs) with siRNA targeting CaSR or pharmacologic inhibition (NPS 2143, 1hr incubation) of CaSR reversed the hyperoxia‐induced AHR and the contractile responses were normalized to control level, with hyperoxic groups Emax of 44.0±5.2% and 41.3±3.1%, respectively. AHR was not observed in CaSR knockout mice suggesting resistance to hyperoxia exposure. These data suggest that CaSR plays an important role in the long‐term effects of neonatal hyperoxia on AHR. We speculate that CaSR may be a novel therapeutic target to reverse airway hyperreactivity in former preterm infants who had received prior supplemental O2 therapy.Support or Funding InformationFunding: NIH: HL R01 138402 and NIH R01 HL 056470

Contrasting Reflex Neural Modulation of Muscle Sympathetic Nerve Activity at Rest and During One‐leg Dynamic Exercise in Subjects with and without Heart Failure

We previously showed that muscle sympathetic nerve activity (MSNA) is augmented at rest in patients with heart failure due to reduced ejection fraction (HFrEF), and rises further during mild and moderate dynamic 1‐leg exercise in stark contrast to the drop observed in healthy controls at similar exercise intensities. The reflex mechanisms responsible for this unique response are unknown. We hypothesized that MSNA may be reduced at rest and during exercise in HFrEF by either: 1) stimulating the sympatho‐inhibitory cardiopulmonary baroreceptors by exercising supine rather than upright; or 2) inhibiting the sympatho‐excitatory peripheral chemoreceptors by breathing 32% oxygen (O2). We studied 6 stable, non‐diabetic, medicated HFrEF men ( mean age 58 ± 3 SE [range 46 to 65] years; mean left ventricular ejection fraction 29 ± 4% [range 15–38]); of either ischemic (n=5) or non‐ischemic (n=1) etiology; plus 6 healthy, age matched, medication‐free volunteers (3 women; mean age 58 ± 3 [range 49 to 72]). We assessed peak oxygen uptake (VO2peak ) by open‐circuit spirometry. On a separate day, fibular MSNA (microneurography) was measured at rest and during upright 1‐leg cycling (2 min each unloaded and at 50% of VO2peak). The identical cycling protocol was then repeated during supine exercise (n=5 HFrEF) and again during upright cycling while breathing 32% O2 (n=4 HFrEF). Heart rate and diastolic blood pressure were similar across interventions in both groups but systolic blood pressure was significantly lower in HFrEF vs controls (main effect P=0.01). MSNA was reduced at rest only while supine in control subjects (main effect P=0.01; P=0.01 vs upright). Whereas in HFrEF, both supine posture and supplemental O2 attenuated MSNA burst frequency at rest (main effect P=0.01; P=0.02 vs upright). During exercise, MSNA burst frequency progressively decreased in healthy controls particularly during unloaded cycling (main effect of time P&lt;0.001), and tended to be lower throughout supine cycling (P=0.06 vs upright). By contrast, in HFrEF patients, there was no significant change in MSNA burst frequency during exercise while supine nor with supplemental oxygen (main effect of intervention P=0.51; time P=0.34). Thus, both at rest and during mild cycling exercise, supine posture augments the sympathoinhibitory response in control subjects. However in HFrEF patients, sympathoexcitation at rest can be reduced to a similar extent by either triggering the inhibitory cardiopulmonary baroreflex or abolishing arterial chemoreceptor activation with no further effect during exercise.Support or Funding InformationSupported by Heart and Stroke Foundation of Ontario and Canadian Institutes for Health Research

Oxygen therapy for pulmonary arterial hypertension: We need to rethink and investigate.

Oxygen therapy for pulmonary arterial hypertension: We need to rethink and investigate.

体外式膜型人工肺と血液吸着療法が奏効した界面活性剤中毒に伴う急性呼吸促迫症候群の1例(A case of acute respiratory distress syndrome associated with surfactant poisoning successfully treated with extracorporeal membrane oxygenation and direct hemoperfusion)

要旨 症例は60歳の女性。自殺目的にジェルボール型洗濯洗剤を計3個摂取したが，嘔吐後から呼吸状態と意識レベルの悪化を伴い，血圧低下も呈するようになったため，当院へ搬送となった。摂取した洗剤には約9gの界面活性剤が含まれていた。来院時，リザーバーマスクで酸素8L/min投与下でSpO290%であった。泡沫状の水様痰が著明であったため気管挿管を実施した。胃洗浄および活性炭と下剤の投与を行った後に人工呼吸器管理となった。大量輸液を継続するも，循環不全が進行しノルアドレナリンも開始となった。その後も酸素化維持が困難となりveno–vnenous extracorporeal membrane oxygenation（VV–ECMO）を導入した。VV–ECMO導入後も血管透過性亢進による影響でVV–ECMO流量の安定化が得られず，大量輸液を要する状態が持続したため，活性炭カラムを用いた直接血液灌流（direct hemoperfusion: DHP）を開始した。DHP導入後，ノルアドレナリンの離脱とVV–ECMO流量の安定化が可能となった。第9病日にVV–ECMOを離脱し，第34病日に人工呼吸器から離脱，その後，精神科での加療のため転科となった。今回，界面活性剤中毒に伴う循環不全と急性呼吸促迫症候群に対してVV–ECMOとDHPを導入し救命し得た症例を経験したので報告する。

Oxygen therapy in patients with ST elevation myocardial infarction based on the culprit vessel: results from the randomized controlled SOCCER trial

BackgroundOxygen (O2) treatment has been a cornerstone in the treatment of patients with myocardial infarction. Recent studies, however, state that supplemental O2 therapy may have no effect or harmful effects in these patients. The aim of this study was thus to evaluate the effect of O2 therapy in patients with ST Elevation Myocardial Infarction (STEMI) based on the culprit vessel; Left Anterior Descending Artery (LAD) or Non-LAD.MethodsThis was a two-center, investigator-initiated, single-blind, parallel-group, randomized controlled trial at the Skåne university hospital, Sweden. A simple computer-generated randomization was used. Patients were either randomized to standard care with O2 therapy (10 l/min) or air until the end of the primary percutaneous coronary intervention. The patients underwent a Cardiac Magnetic Resonance Imaging (CMRI) days 2–6. The main outcome measures were Myocardium at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI) as measured by CMRI, and median high-sensitive troponin T (hs-cTnT).ResultsA total of 229 patients were assessed for eligibility, and 160 of them were randomized to the oxygen or air arm. Because of primarily technical problems with the CMRI, 95 patients were included in the final analyses; 46 in the oxygen arm and 49 in the air arm. There were no significant differences between patients with LAD and Non-LAD as culprit vessel with regard to their allocation (oxygen or air) with regards to MSI, MaR, IS and hs-cTnT.ConclusionThe results indicate that the location of the culprit vessel has probably no effect on the role of supplemental oxygen therapy in STEMI patients.Trial registrationSwedish Medical Products Agency (EudraCT No. 2011–001452-11) and ClinicalTrials.gov Identifier (NCT01423929).

Validation of a new predictive model to improve risk stratification in bronchopulmonary dysplasia

We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD). However, there is still a paucity of studies providing scientific evidence to guide future updates of BPD severity definitions. Our goal was to validate a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks postmenstrual age (PMA). We hypothesized that this approach improves BPD risk assessment, particularly in extremely premature infants. This is a longitudinal cohort of premature infants (≤32 weeks PMA, n = 188; Washington D.C). We performed receiver operating characteristic analysis to define optimal BPD severity levels using the duration of supplementary O2 as predictor and respiratory hospitalization after discharge as outcome. Internal validation included lung X-ray imaging and phenotypical characterization of BPD severity levels. External validation was conducted in an independent longitudinal cohort of premature infants (≤36 weeks PMA, n = 130; Bogota). We found that incorporating the total number of days requiring O2 (without restricting at 36 weeks PMA) improved the prediction of respiratory outcomes according to BPD severity. In addition, we defined a new severity category (level IV) with prolonged exposure to supplemental O2 (≥120 days) that has the highest risk of respiratory hospitalizations after discharge. We confirmed these findings in our validation cohort using ambulatory determination of O2 requirements. In conclusion, a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks improves risk stratification and should be considered when updating current BPD severity definitions.

Intermittent maternofetal O2 supplementation during late gestation rescues placental insufficiency-induced intrauterine growth restriction and metabolic pathologies in the neonatal lamb.

Intermittent maternofetal O2 supplementation during late gestation rescues placental insufficiency-induced intrauterine growth restriction and metabolic pathologies in the neonatal lamb.