High Flow Nasal Canula Research Articles

Factors of late respiratory support or oxygen weaning in infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants. This study aimed at identifying factors associated with early or with late or weaning failure from respiratory support or oxygen (O2) in preterm infants with BPD requiring respiratory support or O2 therapy after discharge from the neonatal intensive care unit (NICU). This retrospective study was conducted in the NICU of a tertiary hospital, in infants born before 32 weeks of gestation between 2012 and 2021, and discharged from the NICU with a respiratory support (tracheostomy [TT], invasive ventilation [IV], Non-IV [NIV], continuous positive airway pressure [CPAP], high flow nasal canula [HFNC]) or O2 therapy for BPD. Univariate and multivariate analyses were performed to identify factors associated with early weaning (before 6 months postmenstrual age [PMA]) or late (after 6 months PMA) and weaning failure. Among the 53 infants included (2% TT, 2% IV, 11% NIV, 25% CPAP or HFNC, 60% O2 at NICU discharge), 23 (43%) were weaned from respiratory support or O2 before 6 months PMA and 39 (73%) before 12 months PMA. IV duration during NICU stay and postnatal steroid treatment were identified as factors associated with a late or weaning failure (OR 1.03, p = .04 and OR 4.11, p = .023, respectively). In this study, nearly half of preterm infants with severe BPD were weaned from respiratory support or O2 before 6 months PMA. IV duration and postnatal steroid treatment during NICU stay were associated with a late or weaning failure.

Application of high flow nasal canula in patients with pulmonary edema caused by seawater drowning

To investigate the therapeutic effect of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive positive pressure ventilation (NPPV) on patients with pulmonary edema caused by seawater drowning. A retrospective analysis method was used. Based on the Utstein database of emergency drowning in the First Hospital of Qinhuangdao, the clinical data of patients with seawater drowning pulmonary edema admitted to the emergency medicine department of the First Hospital of Qinhuangdao from January 1, 2019 to December 31, 2022 were collected. The patients were divided into NPPV group and HFNC group according to different ventilation methods. The general data, endotracheal intubation rate in 7 days, arterial blood gas analysis indexes [arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), arterial oxygen saturation (SaO2)] and hemodynamic indexes (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, blood lactic acid) before and after treatment, length of stay in intensive care unit (ICU), oxygen therapy comfort of the two groups were compared. A total of 54 patients were enrolled, including 21 patients in the NPPV group and 33 patients in the HFNC group. There were no significant differences in gender, age, state of consciousness and other general information between the two groups. Compared with NPPV group, the rate of endotracheal intubation in HFNC group within 7 days was significantly lower [24.2% (8/33) vs. 33.3% (7/21), P < 0.05]. Before treatment, there were no significant differences in arterial blood gas analysis and hemodynamics between the two groups. After treatment, the above indexes in both groups were significantly improved compared with those before treatment, and PaO2, SaO2, systolic blood pressure, diastolic blood pressure and mean arterial pressure in HFNC group were significantly higher than those in NPPV group [PaO2 (mmHg, 1 mmHg≈0.133kPa): 93.56±6.37 vs. 82.14±6.25, SaO2: 1.02±0.09 vs. 0.95±0.11, systolic blood pressure (mmHg): 117.37±8.43 vs. 110.42±8.38, diastolic blood pressure (mmHg): 79.43±7.61 vs. 72.21±4.32, mean arterial pressure (mmHg): 92.34±6.32 vs. 85.12±5.38], PaCO2, heart rate and blood lactic acid were significantly lower than those in NPPV group [PaCO2 (mmHg) : 34.26±5.63 vs. 37.24±6.22, heart rate (times/min): 73.38±7.56 vs. 86.25±5.41, blood lactic acid (mmol/L): 1.38±0.36 vs. 2.25±1.14], and the differences were statistically significant (all P < 0.05). In addition, the length of ICU stay in HFNC group was significantly shorter than that in NPPV group (days: 13.30±2.38 vs. 16.27±4.26), and the comfort rate of oxygen therapy was significantly higher than that in NPPV group [66.7% (22/33) vs. 42.8% (9/21)], with statistical significance (all P < 0.05). HFNC can improve the oxygenation of patients with pulmonary edema caused by seawater drowning, improve hemodynamics, reduce the rate of tracheal intubation, shorten the length of ICU stay, and improve the comfort of oxygen therapy, which has certain clinical application value.

Association of Body Mass Index with Multiple Organ Failure in Hospitalized Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

Safety and efficacy of high flow nasal canula in patients with mild hypercapnia

ContextHigh flow nasal canula is usually used for management of acute hypoxemic failure; however, it may have a potential therapeutic benefits in hypercapnia as it can alter tidal volume, end expiratory volume, positive end expiratory pressure, and respiratory rate.AimEvaluate safety and efficacy of application HFNC (high flow nasal canula) for patients with mild hypercapnia.Settings and designA prospective interventional study.Patients and methodsOver six months, thirty eight patients were enrolled, with mild hypercapnia and PH level not less 7.30 and PaCo2 not more 60 mmhg; with applying HFNC, serial checking of arterial blood gases was done. Checkpoints were at 2 h, 12 h, 24 h, and 48 h post application of HFNC. HFNC can be shifted to NIV or invasive MV at any time whenever indicated.ResultsPrimary pulmonary disorder was chronic obstructive pulmonary disorder in (22 patients) and (16 patients) had interstitial lung disease. For PH in overall, mean values had changed from 7.33 until reached 7.37 at 48 h post HFNC with calculation of P value at each checkpoint from baseline value; significant changes were recorded at 24 h and 48 h post HFNC application. A similar observation was observed for PaCO2. No significant changes were observed at any checkpoint for HCO3.ConclusionHigh flow nasal canula is safe in cases with mild hypercapnia with a considerable success rate and a proven high efficacy.Trial registrationClinicaltrials.gov/NCT05948527, Registered 14 July 2023—Retrospectively registered, https://www.clinicaltrials.gov/NCT05948527.

Ventilatory support and inflammatory peptides in hospitalised patients with COVID-19: A prospective cohort trial.

Several studies have shown that SARS-CoV-2 can induce a massive release of cytokines which contributes to disease severity and mortality. Therefore, cytokine levels in the serum may help to predict disease severity and survival in COVID-19 patients. In this prospective trial, 88 patients who were hospitalised for COVID-19 were enrolled. Blood samples for serum peptide measurements were taken at the time closest to hospitalisation, at day 5, 9 and 13 (±1). The concentrations of cytokines (IL-1α, IL-1β, IL-1RA, IL-6, L-7, L-10, IFN-γ and TNF-α), chemokines (CCL-3, CCL-4 and CCL-7) and growth factors (G-CSF, GM-CSF and VEGF) were assessed and correlated with the type of ventilation, occurrence of consolidations on imaging and the level of care. COVID-19 patients (median age 68 years, IQR 55-77) stayed in hospital between 5-171 days. Compared to patients in the general care unit, patients in the intermediate care unit (IMCU) and intensive care unit (ICU) presented significantly elevated serum IL-6 (p = 0.004) and lower IFN-γ levels (p = 0.005), respectively. The peak inspiratory pressure in ventilated patients correlated positively with IL-1RA, G-CSF and inversely with IFN-γ serum levels (all p<0.05). VEGF serum levels inversely correlated with the fraction of inspired oxygen in patients receiving high-flow nasal canula oxygen therapy (p = 0.047). No significant correlation between serum concentrations of the measured peptides and the type of ventilation, occurrence of radiological consolidations or in-hospital mortality has been observed. IL1-RA, IL-6, IFN-γ, G-CSF, CCL-7 and VEGF serum levels could prove helpful as biomarkers to assess disease severity and the need for intensive care in COVID-19 patients.

Early clinical application and prediction of ROX index in patients with high-flow nasal canula oxygen therapy

To investigate the application value of ROX index in evaluating the effect of high-flow nasal cannula oxygen therapy (HFNC) on patients diagnosed with respiratory failure, and to find a simpler and more effective method to observe the efficacy of HFNC. A retrospective cohort study was conducted. Patients who were admitted to department of critical care medicine of the Tianjin Third Central Hospital from April 2020 to August 2022, diagnosed with type I respiratory failure, and treated with HFNC after failure of conventional oxygen therapy were enrolled. Oxygenation index (PaO2/FiO2), fraction of inspired oxygen (FiO2), gas flow rate at the initial time of admission, and pulse oxygen saturation (SpO2), FiO2 and respiratory rate (RR) at 2, 4, 6, 8, 10 and 12 hours of HFNC were collected, and ROX index was calculated. The patients with symptoms and PaO2/FiO2 improved after HFNC treatment and without higher respiratory support lately were defined as HFNC success, while other patients with symptoms worsening and needing follow-up non-invasive positive pressure ventilation (NIPPV) or invasive positive pressure ventilation (IPPV) were defined as HFNC failure. The tendency of changes in the ROX index at each time point was observed. Receiver operator characteristic curve (ROC curve) was plotted to obtain the optimum cut-off value of ROX index for predicting HFNC outcome and the optimal monitoring time point for HFNC. A total of 142 patients were eventually enrolled, among whom 96 patients (67.61%) were in treated with HFNC successfully, while 46 patients (32.39%) were recorded as HFNC failure (39 patients and 7 patients received NIPPV or IPPV, respectively), with an overall intubation rate of 4.93% (7/142). Compared with the HFNC success group, the HFNC failure group had lower PaO2/FiO2 [mmHg (1 mmHg ≈ 0.133 kPa): 208.8±37.3 vs. 235.7±48.3, P < 0.01] and higher initial gas flow rate (L/min: 46.4±3.9 vs. 42.3±4.9, P < 0.01). However, there was no significant difference in gender, age, primary diagnosis, severity of disease, hemoglobin (Hb), C-reactive protein (CRP), and brain natriuretic peptide (BNP) between the two groups. In the HFNC failure group, there were 12 patients (26.09%) received progressive oxygen therapy within 12 hours of HFNC, of which 3 patients (6.52%) occurred within 6 hours, while the other 9 patients (19.57%) occurred after 6 hours. The initial ROX index was not statistically significant between the two groups. Both groups showed a continuous increasing ROX index with longer treatment duration of HFNC, and the ROX index at all of the time points of the HFNC failure group was significantly lower than that of the HFNC success group with statistically significant difference (2 hours: 9.39±2.85 vs. 10.91±3.51, 4 hours: 8.62±2.29 vs. 11.40±3.18, 6 hours: 7.62±1.65 vs. 11.85±3.45, 8 hours: 7.79±1.59 vs. 11.62±3.10, 10 hours: 7.97±1.62 vs. 12.44±2.75, 12 hours: 8.84±2.51 vs. 12.45±3.03, all P < 0.05). The ROC curve analysis showed that the areas under the ROC curve (AUC) of ROX index assessing the effect of HFNC at the time of treating 6, 8 and 10 hours were better than 2, 4 and 12 hours (0.890, 0.903, 0.930 vs. 0.585, 0.738 and 0.829), indicating that the ROX index could determine the efficacy at the early stage of HFNC (within 6 hours). When the optimum cut-off value of ROX index was 8.78, the sensitivity was 90.6%, and the specificity was 76.5%. The ROX index at 6 hours of HFNC has a certain predictive value for the efficacy of HFNC with an optimum cut-off value of 8.78, which can provide clinical health care personnel a method for observing the efficacy of HFNC, and guide the correct selection of oxygen therapy modality at an early stage and timely adjustment of oxygen therapy strategy.

Delayed intubation associated with in-hospital mortality in patients with COVID-19 respiratory failure who fail heated and humified high flow nasal canula

BackgroundAdvanced respiratory support modalities such as non-invasive positive pressure ventilation (NiPPV) and heated and humidified high flow nasal canula (HFNC) served as useful alternatives to invasive mechanical ventilatory support for acute respiratory failure (ARF) during the peak of the SARS-CoV-2/COVID-19 pandemic. Unlike NiPPV, HFNC is a newer modality and its role in the treatment of patients with severe ARF is not yet clearly defined. Furthermore, the characteristics of responders versus non-responders to HFNC have not been determined. Although recent evidence indicates that many patients with ARF treated with HFNC survive without needing intubation, those who fail and are subsequently intubated have worse outcomes. Given that prolonged use of HFNC in patients with ARF might exacerbate patient self-inflicted lung injury, we hypothesized that among those patients with ARF due to COVID-19 pneumonia, prolonged HFNC beyond 24 h before intubation would be associated with increased in-hospital mortality.MethodsThis was a retrospective, multicenter, observational cohort study of 2720 patients treated for ARF secondary to SARS-CoV-2/COVID-19 pneumonia and initially managed with HFNC within the Banner Health system during the period from March 1st, 2020, to July 31st, 2021. In the subgroup of patients for went from HFNC to IMV, we assessed the effect of the duration of HFNC prior to intubation on mortality.Results1392 (51%) were successfully treated with HFNC alone and 1328 (49%) failed HFNC and were intubated (HFNC to IMV). When adjusted for the covariates, HFNC duration less than 24 h prior to intubation was significantly associated with reduced mortality.ConclusionsAmong patients with ARF due to COVID-19 pneumonia who fail HFNC, delay of intubation beyond 24 h is associated with increased mortality

Systemic lupus erythematosus-related acute lung disease.

Systemic lupus erythematosus (SLE) is non-organ specific autoimmune disease with mainly skin, joint, and kidney involvement. SLE-related acute lung disease (ALD) is rare, poorly investigated and can lead to acute respiratory failure. We conducted a retrospective study aiming to describe clinical features, treatments and outcome of SLE-related APD. We retrospectively included all patients with SLE and ALD admitted from November 1996 and September 2018 to La Pitié-Salpêtrière Hospital, after exclusion of viral or bacterial lung infection, cardiac failure or any other alternate diagnosis. During the time of the study, 14 patients with 16 episodes were admitted to our center: female 79%, mean age ± SD at admission 24 ± 11years. ALD was inaugural of the SLE in 70% cases. SLE main organ involvement were: arthritis 93%, skin 79%, serositis 79%, hematological 79%, kidney 64%, neuropsychiatric 36% and cardiac 21%. 11 episodes required ICU admission for a median time of 8days. Chest CT-scan revealed mostly basal consolidation and ground-glass opacities. When available, bronchoalveolar lavage mostly revealed a neutrophilic alveolitis with alveolar hemorrhage in 67% cases. Symptomatic respiratory treatments were: oxygen 81%, high-flow nasal canula oxygen 27%, non-invasive ventilation 36%, mechanical ventilation 64% and venovenous extracorporeal membrane oxygenation 18%. SLE-specific treatments were: corticosteroids 100%, cyclophosphamide 56% and plasma exchange 25%. All patients but one survived to ICU and hospital discharge. Two patients had a relapse of SLE-related ALD but none had interstitial lung disease during follow-up. Systemic lupus erythematosus-related acute respiratory failure is a severe event, mostly occurring at SLE onset, typical harboring a basal consolidation pattern on chest CT-scan and alveolar hemorrhage on BAL pathological examination. Mortality in our cohort is lower than previously reported but these results needs to be confirmed in further larger studies.

MT27 Comparison of High-Flow Nasal Canula and Non-Invasive Mechanical Ventilation in Treating COVID-19 Patients

The World Health Organization has declared COVID-19 a global pandemic in March 2020. Multiple COVID-19 waves are putting tremendous stress on healthcare systems. Evidence showed that high-flow nasal canula (HFNC) reduced the need for mechanical ventilation and shortened the time to clinical recovery among patients with severe COVID-19. This study aimed to assess the effect of using HFNC compared to non-invasive mechanical ventilation (NIV), on adult patients with COVID-19. This retrospective study included patients hospitalized due to COVID-19 between October 2020 to December 2021 with appropriate ICD-10 diagnosis recorded in a commercially available, all-payer administrative database across 300+ hospitals. The identified patients were divided in two cohorts, one being the patients treated with HFNC as the first line respiratory support and another with NIV. Outcomes included all-cause mortality rate and length of stay. Multivariable analyses were performed to adjust for baseline characteristics. Out of 16,534 eligible patients, 4,334 patients received HFNC as the first line respiratory support, whereas 12,200 received NIV. The all-cause mortality rate was 20.24% and 37.14% in the HFNC and NIV group, respectively. After adjusting for baseline characteristics, the all-cause mortality rate in the HFNC group was lower compared to NIV (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.47-0.55; p<0.001). The total length of stay was around 15 days for all patients. No different was observed between groups ( mean difference 0.3 days; 95% CI, -0.27 – 0.92 days; p>0.05). Patients treated with HFNC showed lower mortality rates compared to NIV for hospitalized COVID-19 patients. However, further studies are still needed to better elucidate the clinical and economic benefit of HFNC in COVID-19 patients.

COVID–19肺炎に合併した特発性血小板減少性紫斑病の1例(A case of idiopathic thrombocytopenic purpura complicated by COVID–19 pneumonia)

症例は73歳の女性。咳嗽が出現し近医を受診しCOVID–19と診断された。自宅療養中に呼吸困難が出現し第9病日に当院に救急搬送されCOVID–19中等症IIの診断で入院となった。第18病日に高熱とともに呼吸・循環動態が悪化し，凝固異常が出現した。尿路感染による敗血症性ショックと続発するDICと診断した。挿管・人工呼吸器管理とし同日ICUに入室した。数日で全身状態は改善，昇圧剤も離脱できたが，第23病日に突然血小板が5,000/µLまで低下した。検査所見や臨床経過からヘパリン起因性血小板減少症，敗血症性DIC，血栓性血小板減少性紫斑病などを除外し，特発性血小板減少性紫斑病（idiopathic thrombocytopenic purpura: ITP）と診断した。血小板輸血・免疫グロブリン大量静注療法・トロンボポエチン受容体作動薬を直ちに投与開始したところ，血小板は数日で安全域まで回復した。ITPの標準的治療により重篤な出血症状を出現させることなく適切に治療しえた。COVID–19の経過中に血小板減少を引き起こす病態の一つにITPがある。報告は本邦ではまだ少なく，COVID–19合併ITPの認知度は十分であるとは言えない。COVID–19の治療には抗凝固療法が行われることもあり，ITPのような出血リスクの高い疾患を早期に診断し適切に治療することは重要である。 A 73–year–old woman who was unvaccinated against COVID–19 presented with persistent cough to a local doctor and was found to be positive for COVID–19 antigen the next day. She was rushed to our hospital on the 9th day of her illness due to dyspnea during home care and was diagnosed with moderate COVID–19. Treatment with remdesivir and other drugs was initiated, and the patient’s condition improved temporarily. However, on the 18th day of her illness, she developed high fever, and her respiratory and circulatory status as well as coagulation system worsened. She was diagnosed with septic shock and disseminated intravascular coagulation as a result of urinary tract infection. She was intubated, connected to a ventilator, and admitted to the intensive care unit. We could wean off the catecholamines and she recovered in a few days. However, on the 23rd day of her illness, her platelet count suddenly dropped to 5,000/μL. She was diagnosed with idiopathic thrombocytopenic purpura. She was transfused with platelets and started on immunoglobulin and thrombopoietin receptor agonist. Thereafter, her platelet count normalized within a few days. Subsequently, she was found to be positive for platelet–associated immunoglobulin G. Although there have been few reports in Japan, ITP is one of the diseases that cause thrombocytopenia during course of COVID–19. Since anticoagulation is often used to treat severe COVID–19 pneumonia, early diagnosis and appropriate treatment are important to prevent bleeding complications. 2019年12月に中国湖北省武漢市で最初にCOVID–19患者が報告されて以降，瞬く間に全世界に流行が拡大した。COVID–19は肺炎などの呼吸器症状だけでなく，神経，心臓，腎臓，消化管，眼，血管など多臓器に合併症を引き起こすことが最近の研究でわかってきた 1, 2。またCOVID–19は自己免疫性疾患など免疫系に異常を来す疾患の潜在的な誘因になると考えられている 3。自己免疫性疾患の一つであるITPをCOVID–19発症中に合併したという症例が2021年4月に世界で初めて報告され 4，以降世界では同様の報告が散見されている 5, 6。 本症例ではCOVID–19治療中に突然血小板数の低下が見られ，様々な病態が鑑別に挙がったがITPと診断し，迅速な治療により良好な転帰を得た。我々の知る限り，本邦では初めての重症COVID–19肺炎合併ITPの報告となる。貴重な症例と考え，ここに報告する。 なお，本症例の掲載にあたっては，患者の了承を得ている。また倫理委員会の承諾の必要がない論文であり，個人情報保護法に基づいて匿名化している。 患 者：73歳の女性 主 訴：咳嗽 既往歴：糖尿病（HbA1c 8.0%），脂質異常症 内服歴：なし 生活歴：ADL（activities of daily living）は自立。COVID–19ワクチンは未接種。 現病歴：咳嗽が持続したため近医を受診し，翌日COVID–19抗原検査陽性と判明した。自宅療養中に呼吸困難が出現し第9病日に当院に救急搬送された（Fig. 1）。 Clinical course and treatment after admission to the intensive care unit. Respiratory and circulatory status of the patient improved initially, and her white blood cell count decreased. However, on the 23rd day of her illness, her platelet count suddenly dropped to 5,000/μL, and purpura appeared on her thorax and abdomen. Platelets were transfused and TPO–RA and IVIG were administered; platelet count recovered gradually over a few days. Nad: noradrenaline, AVP: arginine vasopressin, DOA: dopamine, IVIG: intravenous high–dose immunoglobulin therapy, TPO–RA: thrombopoietin receptor agonist 初診時現症：Glasgow coma scale 15（E4V5M6），血圧129/72mmHg，脈拍75/min，呼吸数18/min，体温36.6℃，SpO2 92%（酸素4L/min投与下）。呼吸は努力様で湿性咳嗽あり。両側胸部にcoarse cracklesを聴取した。皮疹なし。両側下腿浮腫なし。 胸部CT：両側肺野に末梢主体，広範囲のすりガラス影あり。 入院後経過（Fig. 1）：COVID–19中等症IIと診断し，入院初日より高流量鼻カニュラ酸素療法（high flow nasal canula: HFNC，FiO2: 0.6，Flow: 30L/min）を開始するとともに，トシリズマブ，デキサメタゾン，レムデシビル，ダルテパリンナトリウムの投与を開始した。広範な肺炎像があり，一時は挿管管理も検討されたが徐々に酸素化が改善したため第17病日にHFNCから鼻カヌラ（酸素4L/分）に変更した。第18病日に突然高熱が出現，意識レベルと呼吸状態も悪化し凝固異常を認めたため（Table 1），同日挿管・人工呼吸器管理としICUに入室させた。尿沈渣で白血球を多数認め，尿路感染による敗血症性ショックと続発するDICと診断しメロペネムを投与開始した。血圧維持のためにノルアドレナリン，バゾプレッシンの投与を要し，デキサメタゾンをヒドロコルチゾンに変更した。ICU入室後は徐々に呼吸・循環動態が改善し，第22病日には昇圧剤の投与も終了した。第18病日に採取した血液培養と尿培養からKlebsiella pneumoniaeが検出され，アンピシリン/スルバクタムにde–escalationを行った。 全身状態は改善傾向であったが，第23病日に突然血小板が0.5万/μLに低下し（Table 1），胸腹部に紫斑が出現した。血小板減少が判明してすぐに血小板を3回再検したがいずれも同値であり，EDTA依存性血小板減少性紫斑病（EDTA dependent pseudothrombocytopenia: EDP）は否定的であった。身体所見や血液検査所見から敗血症性DICや血栓性血小板減少性紫斑病（thrombotic thrombocytopenic purpura: TTP）は除外した。動脈圧ラインにヘパリンを用いており，ヘパリン起因性血小板減少症（heparin induced thrombocytopenia: HIT）の可能性を考慮してヘパリンをアルガトロバンに変更し，ダルテパリンナトリウムも終了した。B型肝炎，C型肝炎，後天性免疫不全症候群，サイトメガロウイルス感染症，梅毒，ヘリコバクターピロリなどITPを誘発する既知のウイルス感染症を示唆する検査所見は認めず，ITPを誘発する頻度の高い薬剤の使用もなかった。骨髄穿刺は出血のリスクが高いと判断し施行しなかったが，総合的にCOVID–19肺炎に合併したITPと臨床診断し，20単位の血小板輸血・IVIG大量療法・トロンボポエチン受容体作動薬（thrombopoietin receptor agonist: TPO–RA）による治療を開始したところ，血小板数は数日で安全域まで回復した。 後日，血小板関連IgGが陽性（1,830ng/107 cell基準値46以下），HIT抗体が陰性（0.6U/mL 基準値1.0m未満）と判明し，ITPと確定診断した。以後ステロイドを漸減し，第37病日に退院した。 これまでCOVID–19には凝固異常や血栓症を含む様々な合併症が報告され，とくに血小板減少に関しては軽症から重症なものを含め最大で36%に合併するという報告がある 7。COVID–19の治療経過中に血小板減少症を引き起こす稀な病態の一つにITPがある。COVID–19は自己免疫性溶血性貧血，小児多系統炎症性症候群，Guillain–Barré症候群など免疫異常を引き起こす疾患を合併することが明らかになってきており，Kewan Tらの研究によるとITPを0.34%に合併したと報告されている 7。ITPは血小板膜蛋白に対する自己抗体が産生され血小板に結合する結果，主として脾臓における網内系細胞での血小板の破壊が亢進し，血小板減少を来す自己免疫性疾患である。ウイルス感染に続発するITPの発症機序としてはウイルス抗原と血小板抗原との抗原交差反応や，ウイルスに対する免疫応答の過剰反応などが考えられている。COVID–19の原因ウイルスであるSARS–CoV–2ウイルスはEBウイルス，サイトメガロウイルス，ヒト免疫不全ウイルスなどと並んでITPの誘因となりうるウイルスと考えられ，上記の機序によって血小板減少を来すと推察される 8。MohammedらのCOVID–19合併ITP患者42名についてまとめた報告によると，COVID–19合併ITPの発生率は女性よりも男性で僅かに多く（54.8%），年齢の分布は40.5〜78.5歳であり，中央値で63歳と高齢者で多かった。また発症時期の中央値は感染後2〜3週間であり 9，一般的な二次性ITPと比較してより重症度が高い傾向があった 10。本症例は73歳の女性で発症23日目に高度の血小板減少が出現していることからこの報告の特徴と一致していた。 ITPの診断は除外診断が主であり，COVID–19合併ITPに関しても同様である。前述の通りCOVID–19患者にはしばしば血小板減少が見られるが，軽度にとどまることが多い。高度の減少が見られる場合やCOVID–19の症状が改善傾向にもかかわらず血小板減少が進行する場合には，EDP，敗血症性DIC，TTP，HIT，感染症，薬剤性血小板減少症（drug–induced immune thrombocytopenia: DITP），自己免疫性疾患，ITPなどの病態を鑑別する必要がある。EDPに関してはCOVID–19が惹起したという報告もあり 11，異なる凝固薬を添加した採血管を用いて再検することが望ましい。敗血症性DICやTTPは血液検査上凝固線溶系の異常やその他の症状を伴うことが多いが，重症COVID–19肺炎では時に鑑別は難しい。キニーネやバンコマイシン，カルバマゼピンなど原因となる頻度の高い薬剤を投与されている患者ではDITPの可能性を考慮する 12。SLEなど自己免疫性疾患では血小板以外の血球も減少することが多く，抗核抗体や抗カルジオリピン抗体などの血液検査も参考となる。COVID–19の治療中には血栓予防のためにヘパリンを使用する場合が多く，HITは重要な鑑別となる。HIT抗体の確認は除外には有用であるが，偽陽性も多く，過剰診断を防ぐためにまずは4T’sクリニカルスコア（血小板減少，血小板減少のタイミング，血栓，血小板減少のほかの原因の４項目をスコア化したもの）で検査前確率を確認することが肝要である。本症例におけるITP診断までの流れをFig. 2に示す。本症例ではHITとITPが鑑別に残ったが，後者をより疑い自己抗体の検査結果を待たずにITPの治療を開始したところ，良好な転帰を得た。 Flowchart of the differential diagnosis from thrombocytopenia to diagnosis of ITP. This flowchart depicts the process from thrombocytopenia to ITP diagnosis. Diseases to be excluded are noted on the left side, and disease characteristics are noted on the right side. EDP: EDTA dependent pseudothrombocytopenia, TTP: thrombotic thrombocytopenic purpura, HIT: heparin–induced thrombocytopenia, DITP: drug–induced immune thrombocytopenia, HBV: hepatitis B virus, HCV: hepatitis C virus, HIV: human immunodeficiency virus, CMV: cytomegalovirus, EBV: Epstein–Barr virus 一般的にITPでは血小板が5万/μL以下になると歯肉出血，鼻出血が出現し，1〜2万/μL以下になると消化管出血，頭蓋内出血などの生命を脅かす重篤な出血症状が出現し始めるため，治療の最大の目標は出血の予防となる。未だCOVID–19合併ITPの治療に関する知見は乏しいが，ITPの標準的治療に準じて行われることが多い 4, 7。第一選択の治療は副腎皮質ステロイドとIVIG大量療法を組み合わせた治療が一般的であり 13，網内系での血小板の貪食および血小板自己抗体の産生を抑制する。二次感染のリスクを防ぐためにステロイドは用量と期間を最小限に抑え，多くのケースでは2週間後を目安に漸減を開始している。出血リスクが高い緊急時には血小板輸血も考慮するが，一般に効果は限定的である。70%以上の患者が上記の治療法に反応を示す 9が，改善が乏しい患者にはセカンドライン治療としてTPO–RAを考慮する。即効性はなく効果が現れるまでに1週間程度を要するが，血小板数を持続的に増加させる効果が期待できる。本症例では元々ステロイドが投与されていたため，IVIG大量療法とTPO–RAの併用にて初期治療を開始した。COVID–19患者は血栓症を起こしやすいため，TPO–RAに関しては慎重に投与を検討すべきという意見もある 14。COVID–19合併ITPの予後は良好と考えられており，治療に反応を示せば1週間以内で血小板は回復することが多い（中央値は約4日）。COVID–19合併ITP患者の全死亡率は約7%であるという報告があり，患者の約2.8%と4.8%がそれぞれ出血イベントとCOVID–19による呼吸不全により死亡したと報告されている 9。稀ではあるがITPが再発した症例も報告されており 14，本症例では退院して3か月後にフォローアップし再発がないことを確認した。 COVID–19にITPが合併することは稀であるが，この世界規模のパンデミックのなか，COVID–19診療に携わる医師が遭遇する可能性はある。本邦ではCOVID–19合併ITPの報告はまだ少なく 15, 16，認知度は十分であるとは言えない。重症COVID–19肺炎の治療には抗凝固療法が行われることも多く，ITPなど出血リスクの高い疾患を早期に診断し治療を開始することは重要である。COVID–19患者に血小板減少が出現した際はITPの合併にも留意する必要がある。 COVID–19治療中にITPを合併した稀な1例を経験した。ITPの標準的治療で出血合併症を来すことなく良好な転帰を得た。 利益相反はない。

Post covid lung fibrosis (PCLF) or post covid lung sequelae (PCLS) in treated case of severe COVID-19 Pneumonia case in Intensive care unit with ventilatory support and home oxygen therapy for twelve weeks

Lung fibrosis is final radiological outcome of COVID-19 pneumonia documented in proportionately majority of cases. Post COVID lung fibrosis is considered as worrisome radiological complication observed during early phase of pandemic. Time trends of final radiological outcome has evolved over months with or without treatment with antifibrotics and steroids. Importantly, Post covid lung fibrosis resolved more than fifty percent cases in six months and nearly in all cases after one year. In this case report we have documented PCLF in 32-year male hospitalized for severe COVID-19 illness with acute hypoxic respiratory failure secondary to ARDS (acute respiratory distress syndrome). He required high flow nasal canula oxygen supplementation with noninvasive ventilatory support for three weeks. He responded to medical treatment such as injection remdesivir, methylprednisolone and low molecular weight heparin injection. He was discharged to home with advice for home oxygen therapy and medicines such as steroids and antifibrotics Nintedanib. He required oxygen for twelve weeks. His chest imaging done at one year shown residual post covid sequel without any cardiopulmonary and exercise performance impact.

1107. A Survey on Remdesivir Use and Antimicrobial Stewardship Restrictions Throughout the COVID-19 Pandemic

Abstract Background Remdesivir (RDV) was the first agent with proven clinical benefit against COVID-19, shortening the time to recovery in a randomized placebo-controlled trial (RCT). Based on this trial, the Food and Drug Administration approved RDV via emergency use authorization. Despite its wide use, RDV remains controversial. Early use of RDV in patients requiring low flow nasal canula has robust evidence. However, benefit in mechanical ventilation (MV), high-flow nasal canula (HFNC) and non-invasive positive pressure ventilation (NIPPV) is conflicting. Multiple studies, most notably the SOLIDARITY and DisCoVeRy trial, have conflicting results on who benefits from RDV. Deploying novel therapeutics in this changing landscape is challenging. We seek to understand RDV practices and the role of antimicrobial stewardship (ASP) in hospitals across the US. Methods A survey was developed and disseminated through Infectious Diseases Society of America (IDSA) IDea network, IDSA Antimicrobial Stewardship Centers for Excellence and the Society for Healthcare Epidemiology messaging boards. Data collected included city, presence of RDV therapeutic restrictions, and RDV use by degree of oxygen needs for each COVID-19 wave. Results A total of 78 responses were collected, representing wide geographic reach in the US (Figure 1). RDV was restricted in 53% of facilities. Hospitals without restrictions commonly used RDV for patients on MV, NIPPV and HFNC, with more use on HFNC than on NC during the first winter, Delta and Omicron waves (Figure 2). Use on MV declined with each surge. Hospitals with RDV restrictions had more use of RDV on NC than all other ordinal scales (Figure 3). Use in MV, NIPPV and HFNC compared to NC declined in the restricted group with each COVID-19 surge. Figure 1.Geographic distribution of hospitals represented in the survey Figure 2. Remdesivir use by oxygen requirements in hospitals without remdesivir therapeutic restrictions. Figure 3 Remdesivir use by oxygen requirements in hospitals without remdesivir therapeutic restrictions. Conclusion A wide gap between evidence-based guidelines and actual practice exists. This gap was wider in hospitals without COVID-19 therapeutic restrictions in place for RDV. In the unrestricted group, RDV was commonly used for MV, HFNC and NIPPV, where robust RCT evidence of benefit is lacking. Though this practice occurred in both groups, the restricted RDV group prioritized RDV use in NC and did so at higher percentages each subsequent COVID-19 surge. ASP restrictions can have an important role in guiding COVID-19 therapy. Disclosures All Authors: No reported disclosures.

Preterm Babies: At the Hospital

Preterm Babies: At the Hospital

301. Use of a multiplex PCR assay for detection of respiratory co-infections in COVID-19 hospitalized non-ICU patients: an ace up a clinician’s sleeve

Abstract Background Bacterial co-infections in COVID-19 patients represent a significant challenge for clinicians and can impact outcomes. Rapid identification of bacterial co-pathogens improves management, and is crucial to avoid inappropriately administered antimicrobials. We evaluated the use of a multiplex PCR assay in the early detection of respiratory co-infections in COVID-19 hospitalized patients. Methods The study included non-ICU patients with high clinical suspicion of respiratory co-infection. Lower respiratory tract samples (sputum/bronchial secretions), were analyzed using BIOFIRE® FILMARRAY® pneumonia panel plus [(bioMerieux, USA), FA]. Specimens were considered as acceptable based on Gram stain. Conventional cultures were also performed. Results A total of 28 samples from 27 patients (20 males, median age 60 years, IQR 49-71) were analyzed. 8/27 patients were intubated, 5 were treated with high flow nasal canula oxygenation and 11 with high or low oxygen mask. 18 patients received dexamethasone. Co-infection was detected in 17/27 patients (62.9%). 11 specimens were collected in less than 48 hours from admission and no target was identified in 6/11. Detected pathogens and AMR genes, per sample tested, are presented in the table. Bacterial pathogens and any AMR genes were detected in 15 and 4 samples, respectively, leading to modifications of antimicrobial treatment. The semi-quantitative results along with patients’ clinical presentation assisted with differentiation of bacterial colonization versus infection, especially in cases where multiple targets were identified. De-escalation was implemented for 12 patients, for whom no co-infection or a viral co-pathogen (n=2) was detected. One patient was co-infected with another Coronavirus; further analysis, using the FA respiratory panel, detected Human coronavirus HKU-1 along with SARS-CoV-2. Median time until discharge or death was 13.5 days (IQR 9-24). Overall mortality was 33.3%. Detected pathogens, microbial load and AMR genes, per sample tested. Conclusion Implementation of FA assay proved effective for the rapid detection of respiratory co-infections in COVID-19 non-ICU patients. Molecular panel-based assays can contribute to timely adaptation of antimicrobial treatment, benefiting patient management and antibiotic stewardship strategies. Disclosures All Authors: No reported disclosures.

REACTIVATION MILIARY TB IN THE SETTING OF POSTINFECTIOUS COVID-19 LUNGS

REACTIVATION MILIARY TB IN THE SETTING OF POSTINFECTIOUS COVID-19 LUNGS

Early Intubation Reduces the Risk of Death Among COVID-19 Patients: An Observational Study

Background: The objective of this study was to find the association of invasive mechanical ventilation, non-invasive mechanical ventilation (N.I.V) and high flow nasal canula (HFNC) with mortality in COVID 19 pneumonia patients with ARDS. This is an observational cohort study conducted among patients those who were infected with COVID19 infection and received ventilator support. Materials and Methods: This study was a single centred, conducted among COVID19 patients, who came to a tertiary hospital in Bhubaneswar, Odisha. All patients admitted with COVID19 infection and received mechanical ventilation in between August 2020 to November 2020 was included in this study. As this is an observational cohort study, any intervention not required. Only, data collectors collected all relevant patient data using an android-based data collection platform. Result: 398 patients were found to be eligible for this study. Among them, only 24.47% patients received invasive mechanical ventilation and rest were on N.I.V (62.77%) and HFNC support (12.77%). 26 patients died among the 92 invasively ventilated patients, whereas the mortality rate among N.I.V group of patients (78.7%) was significantly higher. Increased TLC count, C-Reactive, Protein, Urea, Creatinine, Heart rate, Respiratory rate were mostly associated with increased mortality among non-invasively ventilated patients. Conclusion: Early intubation may decrease the risk of mortality in patients infected with severe COVID19 infection.

Age and respiratory syncytial virus etiology in bronchiolitis clinical outcomes.

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis. Precise and updated information about demographic characteristics, clinical manifestations, and risk factors for severe disease are needed for optimal implementation of upcoming new therapeutic and preventive interventions. The main goals of this study were to define the epidemiology of acute bronchiolitis in hospitalized young children during 5 calendar years in Spain; evaluate the differences in clinical manifestations between children hospitalized with RSV infection and those hospitalized with non-RSV infection; and identify demographic characteristics, clinical parameters, and risk factors associated with disease severity. We performed a retrospective review of the medical records of children younger than 2 years who were hospitalized with bronchiolitis between January 2015 and December 2019. We constructed multivariable models to identify independent predictors of disease severity defined as length of hospital stay (LOS), pediatric intensive care unit (PICU) admission, and need for a high-flow-nasal canula (HFNC). From January 2015 to December 2019, 1437 children were hospitalized with bronchiolitis and met the inclusion criteria. The proportion of children hospitalized with bronchiolitis caused by RSV increased significantly during the study period, from 60% to 65% (P= .03). The children with RSV bronchiolitis were younger than those with non-RSV bronchiolitis (median age= 3 months [interquartile range= 1.5-6.5 months] vs 4 months [interquartile range= 2-7.5 months], respectively (P< .01). The children younger than 6 months with RSV bronchiolitis had enhanced disease severity compared with those with non-RSV bronchiolitis, as defined by an LOS of more than 4 days, severity scores, need for an HFNC, intravenous fluids, enteral feeding, and PICU admissions (P< .01). Age younger than 6 months and RSV-positive etiology were independently associated with greater odds of PICU admission, need for an HFNC, and longer LOS. This study identified differences in disease severity between young children with RSV bronchiolitis and those with non-RSV bronchiolitis. These differences are particularly significant in children younger than 6 months, who comprise a group of infants with suboptimal innate immunity to RSV and may benefit from new preventive strategies.

Remdesivir in Very Old Patients (≥80 Years) Hospitalized with COVID-19: Real World Data from the SEMI-COVID-19 Registry.

(1) Background: Large cohort studies of patients with COVID-19 treated with remdesivir have reported improved clinical outcomes, but data on older patients are scarce. Objective: This work aims to assess the potential benefit of remdesivir in unvaccinated very old patients hospitalized with COVID-19; (2) Methods: This is a retrospective analysis of patients ≥ 80 years hospitalized in Spain between 15 July and 31 December 2020 (SEMI-COVID-19 Registry). Differences in 30-day all-cause mortality were adjusted using a multivariable regression analysis. (3) Results: Of the 4331 patients admitted, 1312 (30.3%) were ≥80 years. Very old patients treated with remdesivir (n: 140, 10.7%) had a lower mortality rate than those not treated with remdesivir (OR (95% CI): 0.45 (0.29–0.69)). After multivariable adjustment by age, sex, and variables associated with lower mortality (place of COVID-19 acquisition; degree of dependence; comorbidities; dementia; duration of symptoms; admission qSOFA; chest X-ray; D-dimer; and treatment with corticosteroids, tocilizumab, beta-lactams, macrolides, and high-flow nasal canula oxygen), the use of remdesivir remained associated with a lower 30-day all-cause mortality rate (adjusted OR (95% CI): 0.40 (0.22–0.61) (p < 0.001)). (4) Conclusions: Remdesivir may reduce mortality in very old patients hospitalized with COVID-19.

Impaired Endothelial Function in Convalescent Phase of COVID-19: A 3 Month Follow Up Observational Prospective Study.

Background: Endothelial dysfunction has a role in acute COVID-19, contributing to systemic inflammatory syndrome, acute respiratory distress syndrome, and vascular events. Evidence regarding COVID-19 middle- and long-term consequences on endothelium are still lacking. Our study aimed to evaluate if COVID-19 severity could significantly affect the endothelial function after three months from the acute phase. Methods: We assessed endothelial function in outpatients with previous COVID-19 three months after negative SARS-CoV-2 molecular test by measuring flow-mediated dilation (FMD) in patients categorized according to a four-variable COVID-19 severity scale (“home care”; “hospital, no oxygen”; “hospital, oxygen”; “hospital requiring high-flow nasal canula, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation”). FMD difference among COVID-19 severity categories was assessed with analysis of variance; we further clarified the relationship between FMD and previous COVID-19 severity with multivariate logistic models. Results: Among 658 consecutive COVID-19 subjects, we observed a significant linear trend of FMD reduction with the increase of the COVID-19 category (p < 0.0001). The presence of endothelial dysfunction was more frequent among hospitalized patients (78.3%) with respect to home-care patients (21.7%; p < 0.0001). COVID-19 severity was associated with increased endothelial dysfunction risk (OR: 1.354; 95% CI: 1.06–1.71; p = 0.011) at multivariate binary logistic analysis. FMD showed a significant direct correlation with PaO2 (p = 0.004), P/F ratio (p = 0.004), FEV1 (p = 0.008), and 6MWT (p = 0.0001). Conclusions: Hospitalized COVID-19 subjects showed an impaired endothelial function three months after the acute phase that correlated with pulmonary function impairment. Further studies are needed to evaluate if these subjects are at higher risk of developing pulmonary disease or future cardiovascular events.

Towards Fixed Dosing of Tocilizumab in ICU-Admitted COVID-19 Patients: Results of an Observational Population Pharmacokinetic and Descriptive Pharmacodynamic Study.

Background and ObjectiveIn the randomized controlled trial REMAP-CAP, it was shown that next to dexamethasone, the interleukin (IL)-6 receptor antagonist tocilizumab improves outcome, including survival in intensive care unit (ICU)-admitted coronavirus disease 2019 (COVID)-19 patients. Therefore tocilizumab has been added to many COVID-19 treatment guidelines. Because obesity is a risk factor for the development of severe COVID-19, concerns have been raised about overtreatment, as well as undertreatment, through weight-based dosing of tocilizumab. The currently applied dose of 8 mg/kg is based on the use of this drug for other indications, however it has not formally been investigated for COVID-19. In this study, the pharmacokinetics and pharmacodynamics of tocilizumab were investigated in ICU-admitted COVID-19 patients.MethodsThis was an open-label, single-centre, observational population pharmacokinetic and descriptive pharmacodynamic evaluation study. Enrolled patients, with polymerase chain reaction-confirmed COVID-19 were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received intravenous tocilizumab 8 mg/kg (maximum 800 mg) within 24 h after admission to the ICU and received dexamethasone 6 mg daily as concomitant therapy. For evaluation of the pharmacokinetics and pharmacodynamics of tocilizumab, all time points from day 0 to 20 days after dose administration were eligible for collection. A nonlinear mixed-effects model was developed to characterize the population pharmacokinetic parameters of tocilizumab in ICU-admitted COVID-19 patients. Covariate analysis was performed to identify potential covariates for dose individualization. For the development of alternative dosing schedules, Monte Carlo simulations using the final model were performed.ResultsOverall, 29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and nonlinear clearance (CL) was developed and validated. Average CL was estimated to be 0.725 L/day, average volume of distribution (Vd) was 4.34 L, maximum elimination rate (Vmax) was 4.19 μg/day, and concentration at which the elimination pathway is half saturated (Km) was 0.22 μg/mL. Interindividual variability was identified for CL (18.9%) and Vd (21%). Average area under the concentration versus time curve from time zero to infinity of the first dose (AUCinf 1st DOSE) was 938 [±190] μg/mL*days. All patients had tocilizumab exposure above 1 μg/mL for at least 15 days. Bodyweight-based dosing increases variability in exposure compared with fixed dosing.ConclusionsThis study provides evidence to support a fixed dose of tocilizumab 600 mg in COVID-19 patients. Fixed dosing is a safe, logistically attractive, and drug expenses saving alternative compared with the current 8 mg/kg recommendation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01074-2.