Improvement Of Hypoxemia Research Articles

Impact of pharmacologic patent ductus arteriosus treatment on acute respiratory and oxygenation metrics in very low birth weight infants.

Hypoxemia and respiratory compromise occur in very low birthweight (VLBW, <1500 grams) infants and may be associated with shunting across a patent ductus arteriosus (PDA). The impact of pharmacologic PDA treatment on acute hypoxemia and respiratory metrics is unclear. To determine whether pharmacologic PDA treatment is associated with acute improvement in hypoxemia and respiratory metrics in VLBW infants. At a single center (2012-2022), all VLBW infants with echocardiographic evidence of a PDA and without exclusions were classified as having received or not received pharmacologic PDA treatment (PDA-T, PDA-NT). Mean daily FiO2 and Respiratory Acuity Score (RAS, PMID 30374050) were compared at baseline (day 0) and 3 days after treatment start. For PDA-T infants with archived 0.5Hz (every-2-second) SpO2 data, mean daily SpO2 and the percentage of time with severe hypoxemia (SpO2 <80%) were compared before and after treatment. Severe hypoxemia was further analyzed after stratification by clinical variables (sex, medication, gestational age, postnatal age). We analyzed 125 VLBW infants with a PDA, of whom 66 received pharmacologic PDA treatment. We analyzed a subgroup of 43 PDA-T infants with every-2-second SpO2 data available. PDA-T infants had higher baseline FiO2 and RAS and lower SpO2 than PDA-NT infants (p<0.05). Compared to baseline, RAS decreased from median 258 (IQR 171, 348) to 254 (IQR 174, 419) three days after the start of treatment (p=0.012), but median FiO2 increased from 37% (IQR 28, 46) to 40% (IQR 29, 52) (p=0.008). SpO2 and the percent time with severe hypoxemia were unchanged. In this 10-year retrospective single-center analysis, pharmacologic PDA treatment in VLBW infants was not associated with a major improvement in acute measures of oxygenation or level of respiratory support.

Use of Multiple Doses of Intravenous Infusion of Umbilical Cord-Mesenchymal Stem Cells for the Treatment of Adult Patients with Severe COVID-19-Related Acute Respiratory Distress Syndrome: Literature Review.

Acute respiratory distress syndrome (ARDS) is a critical complication in severe COVID-19 patients. The intravenous infusion (IVF) of umbilical cord- (UC-) mesenchymal stem cells (MSCs), validated to substantially reduce the release of several inflammatory cytokines in vivo, was also shown to exhibit benefits in improving hypoxemia among severe COVID-19 patients. A single dose of IVF-UC-MSCs therapy for severe COVID-19 patients was shown to alleviate the initial ARDS severity, but have 50%-67% case-fatality rates. In Taiwan, few adult patients with severe COVID-19-induced ARDS receiving compassionate adjuvant treatment consisting of either a single dose (1-10 × 106 cells/kg body weight (kg BW)) or three doses (5 × 106 cells/kg BW in each dose) of IVF-UC-MSCs had good outcomes. However, the optimal dosage and rounds of IVF-UC-MSCs administration for the treatment of severe COVID-19 patients with ARDS are undetermined. We reviewed the 2020-2022 PubMed literature database concerning the clinical efficacy of IVF-UC-MSCs among severe COVID-19 patients. The data of COVID-19 case series in the PubMed literature revealed a notable heterogeneity in the therapeutic dosage (a single dose: 1-10 × 106 cells/kg BW; and three doses: 50-200 × 106 cells/kg BW in each dose) and the post-ARDS days of IVF-UC-MSCs administration (a single dose: 1-12; and multiple doses: 5-14) for the treatment of severe COVID-19-associated ARDS. The survival rates among these severe COVID-19 patients ranged from 50% to 76%. However, an overall rate of 93.1% of significant improvement in hypoxemia was observed for the COVID-19 survivors receiving IVF-UC-MSCs at the initial ARDS stage. According to our analysis, the ideal treatment dosage of IVF-UC-MSCs for severe COVID-19-induced ARDS is likely 5 × 106 cells/kg BW for three cycles within 5 days of ARDS onset in severe COVID-19 patients.

Is Intermittent Abdominal Pressure Ventilation Still Relevant? A Multicenter Retrospective Pilot Study

Non-invasive ventilatory support (NVS) is a technique used to reduce respiratory work in neuromuscular diseases, preventing the progression of respiratory failure. NVS is usually administered via a nasal or an oronasal mask, causing discomfort, especially in patients ventilated for more than 16 h/day. Intermittent abdominal pressure ventilation (IAPV) differs completely from conventional NVS and consists of a portable ventilator and a corset with Velcro closures as the interface. In our study, the practicability and efficacy of IAPV were studied in three Italian centers monitoring 28 neuromuscular patients using IAPV who were then retrospectively analyzed. The primary outcomes were an improvement in hypoxemia and the normalization of hypercapnia, and the secondary outcome was an improvement in quality of life. Data were collected at baseline (T0) and after two hours of ventilation (T1), with follow-ups at three months (T2) and six months (T3). Statistical significance was found for PaCO2 over time (F (2.42) = 7.63, p = 0.001) and PaO2 (W = 0.539, p = 0.033). The time of NVS usage also significantly affected the quality of life (F (2.14) = 6.90, p = 0.010), as seen when comparing T0 and T3. As an alternative ventilation method, IAPV is still relevant today and could become a key part of daytime support, especially for patients who do not tolerate standard daytime NVS with an oral interface.

Efficacy Analysis of High-flow Nasal Oxygen Therapy in Patients Accepting Single-port Video-assisted Thoracoscopic Lobectomy

背景与目的部分胸外科患者术后拔除气管插管后并发低氧血症，常表现为Ⅰ型呼吸衰竭，改善低氧血症是促进患者术后康复的重要因素之一。本研究通过比较经鼻高流量湿化氧疗（high-flow nasal oxygen therapy, HFNO）、无创辅助通气（noninvasive mechanical ventilation, NIMV）及鼻导管吸氧（nasal oxygen breath, NOB）在单孔胸腔镜下肺叶切除术后并发低氧血症患者中的应用，探讨不同吸氧方式的优缺点，进一步探究HFNO在该类患者中的治疗效果。方法选取2021年6月-2022年3月在苏州大学附属第二医院接受单孔胸腔镜下肺叶切除术后并发低氧血症的患者180例，随机分为三组（n=60），分别采用HFNO、NIMV及NOB治疗。观察各组患者使用前、使用1 h、使用6 h-12 h及停止使用后的动脉血气分析结果、患者舒适度以及并发症发生率，并使用SPSS 25.0软件进行统计分析，P < 0.05为差异有统计学意义。结果对于单孔胸腔镜下肺叶切除术后并发低氧血症的患者，HFNO的治疗效果不逊于NIMV（P=0.333），相较于NOB，HFNO与NIMV均可较快提升患者的氧合指数（partial pressure of oxygen/fraction of inspiration O2, PaO2/FiO2）（P < 0.001）。除此之外，HFNO在患者使用舒适度、住院时间方面表现出绝对优势（P < 0.001, P=0.004），术后并发症较其他两组略有降低（P=0.232），但对于术后低氧血症并发动脉血二氧化碳分压（partial pressure of carbon dioxide, PaCO2）升高的患者，HFNO的治疗效果仍稍逊色于NIMV。结论对于单孔胸腔镜下肺叶切除术后并发低氧血症的患者，HFNO可作为首选治疗方式；但对于术后低氧血症伴随PaCO2升高的患者，仍推荐使用NIMV改善氧合。

Programmed multi-level ventilation in COVID-19-related acute respiratory distress syndrome: a multi-center retrospective observational study.

ObjectiveWe evaluated pressure-controlled ventilation (PCV) with multiple programmed levels of positive end expiratory pressure (programmed multi-level ventilation; PMLV) in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS).MethodsWe conducted a multicenter, retrospective study from November 2020 to February 2021. PMLV was used with PCV in all patients with intensive care admission until improvement in oxygenation (fraction of inspired oxygen [FiO2] ≤0.50 and oxygen saturation [SpO2] >92%). The observed outcomes were improvement of hypoxemia, length of mechanical ventilation, partial pressure of carbon dioxide (PaCO2) stability, and adverse events.ResultsOf 188 mechanically ventilated patients with COVID-19-related ARDS, we analyzed 60 patients treated with PMLV. Hypoxemia improved in 55 (92%) patients, as measured by the change in partial pressure of oxygen/FiO2 and SpO2/FiO2 ratios on day 3 versus day 1, and in 32 (66%) ventilated patients on day 7 versus day 3. The median (interquartile range) length of mechanical ventilation for survivors and non-survivors was 8.4 (4.7–14.9) and 6.7 (3.6–10.3) days, respectively.ConclusionsPMLV appears to be a safe and effective ventilation strategy for improving hypoxemia in patients with COVID-19-related ARDS. Further studies are needed comparing the PMLV mode with the conventional ARDS ventilatory approach.

Spontaneous Heparin-Induced Thrombocytopenia and COVID-19 Infection

Background and Objective: Heparin-induced thrombocytopenia (HIT) can develop if immune responses to infections become pathologic in the presence of heparins. Low molecular weight heparin or unfractionated heparin are recommended for prophylaxis and treatment of venous thromboembolic disease in hospitalized patients with Covid-19 infection but may trigger HIT. Our aim is to alert clinicians that HIT occurs in association with Covid-19 infections even in the absence of prior exposure and may not be easily recognized without a high index of suspicion. Case Summary: A 33-year-old previously healthy male was initially evaluated for low grade fever, dyspnea without hypoxia and cough. A Covid-19 PCR swab was negative despite a recent exposure. He was treated with azithromycin. However, his symptoms did not improve, he then developed right leg swelling and hypoxia, so he was re-evaluated. CTA of the chest showed bilateral pulmonary emboli and ground-glass opacities at the lung bases. Venous Duplex Ultrasound showed non-occlusive thrombus in the deep veins of right lower extremity. He was hospitalized and placed on oxygen and heparin. Covid-19 swab was negative again. Laboratory tests before heparin showed a decreased platelet count of 64,000 k/ul, elevated prothrombin time of 16.4 seconds, normal aPTT at 30.8 seconds, decreased serum fibrinogen at 120 mg/dl and markedly elevated D-dimer at 59,966 ng/ml. Lupus anticoagulant and anti-phospholipid antibody tests were negative. On heparin at the desired therapeutic aPTT target range, the right leg became significantly swollen and painful by day five. Platelet count had decreased further to 39,000 k/ul. Repeat doppler examination of the right leg now showed more severe and extensive deep venous thrombosis. D-dimer had increased to 125,133 ng/ml. The HIT 4T score was 4, suggesting intermediate probability. Rapid HIT immunoassays on 2 separate samples were positive. Heparin was discontinued and he was placed on argatroban. Serotonin release assays on 2 separate samples came back positive. Suspicion for Covid-19 infection remained high and so a Covid-19 serology sample was obtained which was positive for IgG. A repeat nasopharyngeal swab at this time turned positive. He did not receive any COVID specific treatments. As viability of his leg appeared threatened, he underwent right iliofemoral vein thrombectomy with arteriovenous fistula creation. He improved on argatroban and was transitioned to apixaban with gradual normalization of hemostasis laboratory parameters, improvement in hypoxemia and fading clinical symptoms, he was discharged home on day 15. Conclusion: Current consensus guidelines for thromboprophylaxis and treatment of thromboembolism in hospitalized patients with Covid-19 infection recommend heparins as primary therapy to reduce morbidity and mortality. However, our report in addition to the two previous reports of HIT in Covid-19 patients illustrate that HIT can be a complication in the setting of Covid-19 infection. Further, our report also highlights that HIT with thrombosis can occur in a spontaneous manner in the absence of prior heparin exposure, which has been so far studied only in bacterial infection with the hypothesis that Platelet factor 4 (PF4) can bind to negatively charged polysaccharides on the surface of bacteria, triggering an immune response. DisclosuresNo relevant conflicts of interest to declare.

Is bilevel PAP more effective than CPAP in treating hypercapnic obese patients with COPD and severe OSA?

Commentary on Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP versus bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 20XX;XX(XX):XXX-XXX. doi:10.5664/jcsm.9506.

Effects of prone positioning during extracorporeal membrane oxygenation for refractory respiratory failure: a systematic review.

As more and more studies have shown that venovenous extracorporeal membrane oxygenation (VV-ECMO) improves oxygenation and prognosis of critical patients, VV-ECMO has been frequently used in critical patients for severe acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a postural therapy for ARDS, which permits for better ventilation/perfusion ratio (V/Q) matching, improvement of hypoxemia. Some articles revealed that performing PP during ECMO for refractory respiratory failure is feasible; however, the results obtained were controversial. Therefore, we performed a systematic review to further assess the effects of PP during ECMO for refractory respiratory failure. Six studies with 465 subjects were enrolled. Four articles examined changes of PaO2/FiO2 ratio after PP during VV-ECMO; PaO2/FiO2 ratio improved from 18.5 to 62 mmHg. Our analysis inferred that the PP-ECMO group did not have a significant advantage in survival at discharge (odds risk 1.42, 95% confidence interval 0.92–2.18; p = 0.11) compared with the ECMO group. We found that the PP-ECMO group had a significantly longer duration than the ECMO group (MD 5.37, 95% CI 4.19–6.54, I2 = 67%, P < .00001). ICU length of stay in the PP-ECMO group was significantly longer than the ECMO group (MD 7.29, 95% CI 4.06–10.52, I2 = 64%, P < .00001). No unplanned extubation of ECMO was recorded. In conclusion, our review found that performing PP during ECMO for refractory respiratory failure is safe and PP can improve the PaO2/FiO2 ratio, which is in line with the length of PP performed.

What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak.

Tocilizumab, an interleukin-6 receptor blocker, has been used in the inflammatory phase of COVID-19, but its impact independent of corticosteroids remains unclear in patients with severe disease. In this retrospective analysis of patients with COVID-19 admitted between March 2 and April 14, 2020 to a large academic medical center in New York City, we describe outcomes associated with tocilizumab 400 mg (without methylprednisolone) compared to a propensity-matched control. The primary endpoints were change in a 7-point ordinal scale of oxygenation and ventilator free survival, both at days 14 and 28. Secondary endpoints include incidence of bacterial superinfections and gastrointestinal perforation. Primary outcomes were evaluated using t-test. We identified 33 patients who received tocilizumab and matched 74 controls based on demographics and health measures upon admission. After adjusting for illness severity and baseline ordinal scale, we failed to find evidence of an improvement in hypoxemia based on an ordinal scale at hospital day 14 in the tocilizumab group (OR 2.2; 95% CI, 0.7-6.5; p = 0.157) or day 28 (OR 1.1; 95% CI, 0.4-3.6; p = 0.82). There also was no evidence of an improvement in ventilator-free survival at day 14 (OR 0.8; 95% CI, 0.18-3.5; p = 0.75) or day 28 (OR 1.1; 95% CI, 0.1-1.8; p = 0.23). There was no increase in secondary bacterial infection rates in the tocilizumab group compared to controls (OR 0.37; 95% CI, 0.09-1.53; p = 0.168). There was no evidence to support an improvement in hypoxemia or ventilator-free survival with use of tocilizumab 400 mg in the absence of corticosteroids. No increase in secondary bacterial infections was observed in the group receiving tocilizumab.

INTRATRACHEAL SALINE BOLUS INCREASES SURVIVABILITY IN RABBITS EXPOSED TO LETHAL DOSE OF INHALED HYDROGEN SULFIDE

SESSION TITLE: Pharmacotherapeutics Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Hydrogen Sulfide (H2S) is a highly toxic, flammable, and colorless gas. In addition to industrial accident risks, H2S has been identified as a potential terrorist chemical and military threat agent for use in mass-casualty events, with no effective antidotes. In this study, we investigate the effects of a small volume of intratracheal (IT) slow-drip saline versus IT fast bolus saline treatment to prolong survival in H2S exposure in an animal model for potential treatments during mass-casualty crises. METHODS: The effects of IT saline in H2S exposure were tested on 49 New Zealand white male rabbits. Animals were anesthetized and intubated, but not ventilated. H2S gas (2000 ppm) was delivered along with a 1.5% isoflurane in air mixture (2.25 liters/min)for 30 minutes.Three groups were compared: no saline into endotracheal tube control(n=16), IT slow saline drip (n=17) and fast IT saline bolus group (n=16). Animals in IT slow drip saline group received 3cc of saline in 3 minutes, while fast saline bolus group animals received it in less than 20 seconds. Both treatment groups were compared to the control group. Systemic blood pressure and heart rate were continuously monitored.The changes in tissue oxy and deoxy hemoglobin concentrations were measured non-invasively over the brain region using continuous wave near infrared spectroscopy. Animals were deemed survivors at 60 minutes from the start of toxic exposure. Animals were sacrificed when systolic blood pressure dropped below 20 mmHg. RESULTS: The average weight for all animals(n=49) in this study was 3.88 ± 0.35 kg, mean ± SD. The survival rate of the fast saline, slow saline, and the control groups were 56.25%, and,23.53%, and 25%.Log-rank (Mantel-Cox) test showed that the survivability in the treatment groups and control groups are significantly different (p=0.0417). Slow saline group versus fast saline group difference was also significant (p=0.0140). The slow saline group compared to control group results were not different (p=0.7031). CONCLUSIONS: The rapid administration of a small volume of saline bolus given via IT route was effective in prolonging survival in lethal H2S exposure when given rapidly. These findings appear likely due to the rapid bolus stimulating cough and breathing responses in apneic animals, in contrast to the slow dripping of a similar amount of saline.While the stimulation of breathing leads to inhalation of more H2S in this model, improvement in hypoxemia in these animals appears to be of greater importance than the risk of additional H2S exposure.Thus, we propose that the hypoxemia from H2S-induced respiratory depression is a major contributor to mortality compared to the metabolic inhibition of cytochromes from H2S in this scenario. CLINICAL IMPLICATIONS: This has potential implications for the treatment victims of H2S exposure who cannot be removed from the exposure site as this commonly occurs in mass-casualty events. DISCLOSURES: No relevant relationships by vikhyat bebarta, source=Web Response No relevant relationships by Gerry Boss, source=Web Response No relevant relationships by Matthew Brenner, source=Web Response No relevant relationships by Tanya Burney, source=Web Response No relevant relationships by Adriano Chan, source=Web Response No relevant relationships by Melina Doosty, source=Web Response No relevant relationships by Philippe Haouzi, source=Web Response No relevant relationships by Tara Hendry-Hofer, source=Web Response No relevant relationships by Jangwoen Lee, source=Web Response No relevant relationships by Sari Mahon, source=Web Response No relevant relationships by David Mukai, source=Web Response No relevant relationships by George Philipopoulos, source=Web Response

EMERGENT THROMBECTOMY OF HIGH RISK PE

SESSION TITLE: Fellows Pulmonary Vascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Some physiologic consequences of high risk pulmonary emboli (PE), such as shock and refractory hypoxemia, require urgent reperfusion therapy. Delaying management in those cases may lead to catastrophic consequences including hemodynamic collapse. However, comorbid conditions often limit treatment options complicating management. Here we present two cases of acute onset severe hypoxemia attributable to PE. Neither patient was a candidate for pharmacological thrombolysis due to recent or active GI bleeding. CASE PRESENTATION: Patient A, a 52-year-old male with prior colectomy due to ulcerative colitis, was admitted with duodenal perforation and post-ERCP pancreatitis with one day of significant dyspnea and hypoxemia. He underwent testing with a computed tomography pulmonary angiogram (CTPA) which revealed pulmonary emboli. Despite intubation, FiO2 of 100%, recruitment maneuvers, and inhaled vasodilator therapy with epoprostenol, he had persistent and refractory hypoxemia (Table). After the initiation of heparin, he had recurrent gastrointestinal hemorrhage and required vasopressors. Patient B, a 71-year-old female with multiple myeloma and on chemotherapy with pancytopenia and lower GI bleed two weeks prior, presented with acute onset of dyspnea for less than one day and high oxygen requirements and labile hemodynamics with signs of hypoperfusion (Table). CTA confirmed pulmonary emboli. Point of care ultrasonography demonstrated signs of right heart strain. DISCUSSION: Both patients had bilateral pulmonary emboli and filling defects in distal left main pulmonary artery extending into left upper and lower lobar arteries and lobar and segmental arteries on the right. After rapid discussion with a multidisciplinary PE response team, percutaneous aspiration thrombectomy via the FlowTriever System was utilized in both patients. The FlowTriever System is a large bore catheter device which is FDA approved for mechanical thrombectomy in the pulmonary arteries. Both patients were successfully treated with acute clinical and technical success, with intraprocedural improvements of mean pulmonary artery pressures of > 25%. Patient A had immediate improvement of hypoxemia. Patient B had improvement in her hemodynamic stability and organ perfusion. Both patients did require packed red blood cell transfusions. This is partially attributed to both patients having active GI bleeding, but can be exacerbated aspiration of blood during thrombectomy if multiple passes are required. CONCLUSIONS: Percutaneous thrombectomy is an alternative treatment option in critically ill patients with high risk of hemodynamic collapse or refractory hypoxemia, especially in those with contraindications to thrombolysis. One limitation is the possibility of intraprocedural blood loss which should be anticipated and address with volume expansion with or without transfusion. Reference #1: Marshall PS, Mathews KS, Siegel MD. Diagnosis and management of life-threatening pulmonary embolism. J Intensive Care Med. 2011;26(5):275-294. doi:10.1177/0885066610392658 Reference #2: Wible BC, Buckley JR, Cho KH, Bunte MC, Saucier NA, Borsa JJ. Safety and Efficacy of Acute Pulmonary Embolism Treated via Large-Bore Aspiration Mechanical Thrombectomy Using the Inari FlowTriever Device. J Vasc Interv Radiol. 2019;30(9):1370-1375. doi:10.1016/j.jvir.2019.05.024 DISCLOSURES: No relevant relationships by Brian Cody Adkinson, source=Web Response Consultant relationship with Bellerophon Please note: $1001 - $5000 Added 06/01/2020 by Roger Alvarez, source=Web Response, value=Travel Advisory Committee Member relationship with United Therapeutics Please note: $1001 - $5000 Added 06/01/2020 by Roger Alvarez, source=Web Response, value=Consulting fee No relevant relationships by Adhiraj Gosine, source=Web Response No relevant relationships by Susanna Leonard, source=Web Response

PULMONARY HYPERTENSION IN A CHILD WITH STAT3 GAIN OF FUNCTION MUTATION-ASSOCIATED INTERSITIAL LUNG DISEASE

SESSION TITLE: Fellows Pediatrics Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: STAT3 gain of function mutations are a recently described cause of autoimmunity that affect multiple organ systems, including the lungs. CASE PRESENTATION: The patient was first diagnosed with autoimmune lymphoproliferative syndrome (ALPS) at age 2 in the setting of lymphadenopathy, hepatosplenomegaly, & autoimmune cytopenias. Treatment was initially steroids & IVIG; he later started sirolimus as a steroid-sparing agent. No genetic defect consistent with ALPS was identified though he was found to have short telomeres, of unclear significance as he did not fit a dyskeratosis congenita phenotype. Further evaluation revealed a gain of function (GOF) mutation in STAT3. At age 9, he developed dyspnea & syncope; evaluation revealed mild pulmonary hypertension (PH) with positive vasoreactivity testing and CT chest with upper-lobe predominant subpleural cystic lung disease & scattered pulmonary nodules. Immunosuppression was switched from sirolimus to mycophenolate. For the PH, he was prescribed dual oral therapy, with symptomatic improvement. He developed hypoxemia at age 11. VQ scan was notable for markedly heterogeneous perfusion despite homogenous ventilation & PFTs revealed a reduced DLCO with mild restriction. Given concern for worsening pulmonary disease in the setting of the STAT3 mutation, he was started on tocilizumab (in place of mycophenolate) with partial improvement in hypoxemia. At age 12, given persistent oxygen requirement & CT showing new upper lobe predominant mosaic attenuation with groundglass (& overall stable cystic lung disease), he started ruloxitinib with some improvement in his dyspnea & hypoxemia. Since tocilizumab & ruloxitinib were initiated, his TLC & DLCO have normalized. DISCUSSION: In the largest series of patients with STAT3 GOF autoimmunity, 36% were reported to have interstitial lung disease (ILD), though none had cystic lung disease1. Upper-lobe predominant subpleural cystic disease, as seen in our patient, is most reminiscent of that often incidentally found in Trisomy 21, and has not been described in other pediatric populations2. In addition to autoimmunity related to STAT3 GOF involving the lungs, there is evidence that inappropriate activation of STAT3 is involved in the development of fibrosis in patients with UIP/IPF, suggestive of a potential alternative pathway to ILD in these patients3. Pulmonary hypertension has not previously been described as a consequence of STAT3 GOF mutations. Our patient developed PH years before he became hypoxemic, suggestive that his PH is not simply due to chronic hypoxemia. CONCLUSIONS: In this patient, STAT3 GOF mutation was associated with cystic lung disease and pulmonary hypertension, manifestations that have not previously been described. Reference #1: Fabre A, Marchal S, Barlogis V, et al. Clinical aspects of STAT3 gain-of-function germline mutations: a systematic review. J Allergy Clin Immunol Pract. 2019;7(6):1958-69. Reference #2: George M, Amodio J, Lee H. Cystic lung disease in Down syndrome: a case report and literature review. Case Rep Pediatr. 2016;2016:4048501. Reference #3: Pechkovsky DV, Prele CM, Wong J, et al. STAT3-mediated signaling dysregulates lung fibroblast-myofibroblast activation and differentiation in UIP/IPF. AJP. 2012;180(4):1398-1412. DISCLOSURES: No relevant relationships by Sarah Cohen, source=Web Response No relevant relationships by Stephen Kirkby, source=Web Response

Clinical manifestations and progression of COVID‑19: A case report from the Maldives

A cluster of pneumonia was reported from Wuhan, Hubei province, China in December 2019. The causative agent was named as novel coronavirus “SARS-CoV-2” and the disease as COVID-19. The disease rapidly spread to several countries and WHO declared the outbreak as a Public Health Emergency of International Concern and as a pandemic on 11th March 2020. In the Maldives, the first case of COVID-19 was detected on the 7th of March. At the time of writing, there are 3103 cases of confirmed COVID-19 including 15 fatalities. The SARS-CoV-2 causes mild to severe pneumonia complicated by ARDS, sepsis, and multi-organ dysfunction syndrome. Other manifestations include anosmia, ageusia, fatigue, and rash. In many requiring hospitalization, hypoxemia is a key clinical finding. The clinical manifestations including the clinical progression of COVID-19 is being described in this report. The case was conservatively managed in a makes-shift hospital, with the utilization of the awake prone positioning which had resulted in better oxygenation and aided in the improvement of hypoxemia.

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Safety of prone positioning in critically ill patients

Background: During the past two years, 5% of patients admitted to the Medical Intensive Care Unit (MICU) of Hamad General Hospital (HGH) had severe acute respiratory distress syndrome (ARDS) with a PaO2/FiO2 ratio less than 100 mmHg. The risks associated with this condition include ventilator associated lung injury, over distension of lungs, and poor gas exchange which results in increased morbidity and mortality. With quality improvement initiatives like prone positioning, the mortality and morbidity associated with severe acute respiratory syndrome1 can be reduced by improving hypoxemia2 with a significant enhancement in PaO2/FiO2 ratios while reducing injurious ventilation. Also, prone positioning can help prevent invasive interventions such as placing patients on extracorporeal membrane oxygenation (ECMO) therapy.3 Methods: We evaluated the safety of prone positioning for improving hypoxemia in critically ill patients with PaO2/FiO2 ratio < 100 mmHg to PaO2/FiO2 ratio < 200 mmHg from 1st January 2017 to 31st December 2018, without major complications. Data collected included the PaO2/FiO2 ratios based on arterial blood gases of mechanically ventilated patients before and after prone positioning.We were able to facilitate prone positioning in 72 out of 110 patients with severe ARDS having a total average PaO2/FiO2 ratio of 84.4 ± 30 mmHg. The patients were proned for a maximum of 16 hours in each session where up to three sessions were incorporated. No major complications were encountered during the proning sessions. This was thought to be accomplished through the coordination of a dedicated multidisciplinary team, education and simulation classes for physicians, nurses, and respiratory therapists, following appropriate inclusion and exclusion criteria for prone positioning, and implementing quality measures through Plan-Do-Study-Act (PDSA) cycles as represented in Figure 1. Results: The total average PaO2/FiO2 ratio before proning for 65% of patients (n = 72) with severe acute respiratory distress syndrome4 was 84.4 ± 30 mmHg and after one hour of 16 hours proning, it improved to 180.3 ± 78 mmHg. The remaining 35% of patients either had traumatic fractures, unstable spinal injury, severe hemodynamic instability, or morbid obesity together with ARDS which made them unfavorable for prone positioning. Out of those who were proned, 11 (12.5%) patients did not have improvement in oxygenation after proning due to non-recruitable lungs and were put on ECMO. The PaO2/FiO2 ratios before and after one hour of implementing the prone position technique in each quarter of 2017 and 2018 are represented in Figure 2. Conclusion: In patients with severe ARDS, prone positioning proves to be a safe practice and leads to improvement in hypoxemia without major complications. Our future prospects with respect to prone positioning include the following:• Sustaining and standardizing the accomplished work of data collection.• Implementing the prone positioning technique across other critical care units of Hamad Medical Corporation.• Keeping a record of minor complications associated with prone positioning and resolving them in further sessions.• Documenting cases with contraindications to prone positioning.

DIFFUSE ALVEOLAR HEMORRHAGE ASSOCIATED WITH FLECAINIDE

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Diffuse alveolar hemorrhage (DAH) occurs as a result of endothelial alveolar-capillary cell injury. Although there are many etiologies for DAH, up to 10% of cases are due to drug toxicity. To our knowledge, we describe a rare case of flecainide-associated DAH likely with underlying diffuse alveolar damage (DAD). Dyspnea and hypoxia improved after cessation of flecainide and initiation of glucocorticoids. CASE PRESENTATION: A 59-year-old female with atrial fibrillation on chronic flecainide presented with a history of dyspnea and dry cough. Vital signs on admission showed hypoxemia with oxygen saturation of 89% on room air. Exam revealed diffuse expiratory wheezing. Chest radiograph showed diffuse interstitial disease with bibasilar lung opacification. She was managed as a case of community acquired multifocal pneumonia, however, remained hypoxemic requiring high flow nasal cannula refractory to antibiotics. Chest computed tomography (CT) demonstrated multifocal areas of ground glass opacities with superimposed interlobular septal thickening in a “crazy paving” pattern (Image 1). During hospitalization, patient developed worsening hypoxemia requiring BiPAP and was transferred to the ICU. Infectious, rheumatologic, and cardiac workup were negative. She was started on intravenous methylprednisolone while in the ICU for presumed ILD. Bronchoscopy was done and bronchoalveolar lavage (BAL) revealed progressively more bloody return in different aliquots consistent with DAH. A literature search showed flecainide linked to DAH and this was discontinued. Steroids were tapered down during a lengthy hospital course with progressive improvement in hypoxemia. Repeat CT of the chest showed significant improvement of ground glass opacities (Image 2). Patient was seen in outpatient clinic after she had a third CT chest performed. This showed further improvement in the ground glass opacities with bibasilar distribution of subpleural reticulation suggestive of underlying DAD with resultant fibrosis (Image 3). PFT’s further confirmed this with a significantly reduced diffusing capacity of 26%. DISCUSSION: There are numerous reports of drug-induced lung injuries and DAH. There have been a few case reports of lung toxicity associated with flecainide, which is felt to be secondary to a cell-mediated immunologic reaction, and is a diagnosis of exclusion. In our case, the patient presented with hypoxemic respiratory failure while on flecainide. Improvement was achieved after withdrawal of flecainide and initiation of steroids, supporting a drug-induced etiology over others. CONCLUSIONS: Our case highlights a rare but potentially lethal manifestation of flecainide-induced pulmonary toxicity. Early recognition of this may prevent irreversible damage leading to pulmonary fibrosis. Reference #1: Hanston P, Evrard P, Mahieu P, Wallemacq P, Friob M, Hassoun A: Flecainide-associated interstitial pneumonitis. Lancet 1991;337:371–372. DISCLOSURES: No relevant relationships by Tracy Ashby, source=Web Response No relevant relationships by Nimeh Najjar, source=Web Response No relevant relationships by Tiara Ong, source=Web Response No relevant relationships by Vandana Seeram, source=Web Response

P4675The utility of additional balloon pulmonary angioplasty for residual hypoxemia in normohemodynamic chronic thromboembolic pulmonary hypertension patients after invasive treatments

Abstract Background Balloon pulmonary angioplasty (BPA) improves hemodynamics, symptoms and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA). However, certain patients still have hypoxemia after BPA or PEA despite normalization of hemodynamics. In CTEPH, hypoxemia is related increased dead space ventilation caused by vascular obstruction. Purpose This study was aimed to clarify whether additional BPA can improve hypoxemia of CTEPH patients after normalization of hemodynamics. Methods A total of 335 patients who underwent initial series of BPA in our institute were followed up. Sixty-four patients with mean pulmonary artery pressure (mPAP) &lt;30mmHg and percutaneous oxygen saturation (SpO2) &lt;95% without oxygen inhalation at more than 6 months after the initial series of BPA and of patients who could reevaluate hemodynamics and oxygenation after additional BPA were enrolled. These patients were divided into two groups with or without additional BPA procedures. Change of hemodynamics and SpO2 were retrospectively investigated. Results Thirty-three of 64 patients underwent additional BPA procedures. Patients' age was older in BPA group than those in non-BPA group (71.3±10.4 vs. 66.5±9.4 years old, p=0.02). mPAP and pulmonary vascular resistance (PVR) was significantly higher in BPA group (mPAP: 23.9±3.2 vs. 20.7±3.8 mmHg, p=0.001, PVR: 4.2±1.2 vs. 3.5±1.4 wood unit, p=0.03, respectively). Among the 1.8±1.4 BPA procedures per person, total 6.6±3.8 segmental pulmonary arteries per person were treated. While no obvious improvements were observed in non-BPA group, PVR and SpO2 in BPA group were significantly improved (4.2±1.2 to 3.7±1.3 wood unit, p=0.002, 90.7±3.1% to 94.1±3.6%, p&lt;0.001, respectively). In the multivariate logistic regression analysis, additional BPA procedures were associated with further improvement of SpO2 (hazard ratio, 3.7; 95% confidence interval, 1.2–11.5; P=0.02). Conclusions Additional BPA procedure was associated with improvement of hypoxemia in CTEPH patients after normalization of hemodynamics. Treating as many lesions as possible in BPA might relieve the patients' residual dyspnea.

Respiratory Failure Secondary to T Cell Lymphoma

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 4 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: ALK positive T cell lymphoma is aggressive albeit chemotherapy responsive. It presents in 0.25 cases per 100,000 people with a 2:1 male to female ratio. It rarely metastasizes to the lungs, and may present with several radiographic findings including a single mass, a nodule with halo sign, bronchovascular distribution, and diffuse reticulation. Early diagnosis and treatment is imperative as the disease can cause respiratory failure. CASE PRESENTATION: 26 year old in excellent health deployed to the Middle East developed an upper respiratory tract infection with axillary adenopathy. Despite two weeks of treatment, he did not improve. X-ray revealed pneumonia. Antibiotics were initiated for persistent fevers and leukocytosis. He was sent to Germany where computed tomography scan revealed diffuse patchy alveolar opacities. Hypoxemia ensued, he was intubated and flown to Walter Reed. Treatment escalated for fungal and viral coverage. Bronchoscopy was performed and bronchoalveolar lavage revealed no infectious culprits. Persistent leukocytosis and lack of resolution provided impetus to obtain axillary lymph node biopsy which revealed grade IV anaplastic Large Cell T-cell lymphoma (ACLC). Chemotherapy provided rapid improvement. DISCUSSION: ACLC metastasis to the lung is a rare clinical entity with only three reported cases. Unfortunately, in these cases the diagnosis was only found post mortem. This case was successful because of the multiple opportunities to readdress the etiology at different levels of care. Prior to diagnosis he was had no improvement of hypoxemia or leukocytosis on broad spectrum antimicrobial therapy. Upon arrival to Walter Reed the differential was challenged to include lymphoma which was vindicated on biopsy. He is radiographically cancer free seventeen months after diagnosis and chemotherapy. CONCLUSIONS: Reassessment of the anchored diagnosis and rapid transfer over 6,500 miles allowed this patient a chance for rapid treatment with quick clinical improvement. Despite the high rate of complete response of this cancer, if missed the outcome appears to be universally fatal. Reference #1: S Ondrejka, DO, et. al. T-cell Lymphomas Updates in Biology and Diagnosis Lung 2015; Surgical Pathology Clinics Reference #2: T Ueda, MD, et. al. Diffuse Pulmonary Involvement by Mycosis Fungoides: High-Resolution Computed Tomography and Pathologic Findings Journal of Thoracic Imaging Reference #3: C Boland, Relapsing T-cell Lymphoma Mimicking Adult Respiratory Distress Syndrome and Sepsis; Leukemia & Lymphoma DISCLOSURE: The following authors have nothing to disclose: Michael Switzer, Paul Clark No Product/Research Disclosure Information

Treatment of Sleep Disordered Breathing Liberates Obese Hypoxemic Patients from Oxygen.

BackgroundObese hypoxemic patients have a high prevalence of sleep disordered breathing (SDB). It is unclear to what extent treatment of SDB can improve daytime hypoxemia.MethodsWe performed a retrospective cohort study of obese hypoxemic individuals, all of whom underwent polysomnography, arterial blood gas analysis, and subsequent initiation of positive airway pressure (PAP) therapy for SDB. Patients were followed for one year for change in partial pressure of arterial oxygen and the need for supplemental oxygen.ResultsOne hundred and seventeen patients were treated with nocturnal PAP and had follow-up available. Adherence to PAP was satisfactory in 60%, and was associated with a significant improvement in daytime hypoxemia and hypercapnea; 56% of these patients were able to discontinue supplemental oxygen. Adherence to PAP therapy and the baseline severity of OSA predicted improvement in hypoxemia, but only adherence to PAP therapy predicted liberation from supplemental oxygen.ConclusionsThe identification and treatment of SDB in obese hypoxemic patients improves daytime hypoxemia. It is important to identify SDB in these patients, since supplemental oxygen can frequently be discontinued following treatment with PAP therapy.

Improvement of Hypoxemia by Inhaled Nitric Oxide Gas Therapy in Potential Deceased Donor

Potential diseased donors manifest altered physiological changes associated with pulmonary edema, profound hemodynamic and metabolic abnormalities. These derangements may be more significant after apnea tests which result in severe hypoxemia and cardiovascular complications. Nitric oxide (NO) inhalation therapy can be applied following apnea tests in the brain-dead donor whose ventilator support has been maintained with high positive end-expiratory pressure. Inhalation of NO gas causes selective dilation of blood vessels in only those lung segments that are actively participating in gas exchange (oxygen and carbon dioxide) at the alveolar capillary level. In other words, this increases the blood flow to areas of the lung where oxygen is being provided and thus improves oxygen levels in the body. We report on the case of a 14-year-old organ donor with inhaled NO therapy after apnea testing. The duration of NO inhalation therapy was 14 hours. This deceased donor, who suffered with severe hypoxemia and hemodynamic instability after apnea tests, improved after NO gas therapy and adequate vasoactive drugs. NO gas therapy will be helpful for improving oxygen delivery to pulmonary vessels. Two kidneys and one liver were successfully retrieved from donors. These recipients had well preserved function of allografts. Therefore, NO inhalation can be help¬ful in improvement of hypoxemia and increasing organ availability in deceased organ donors.