Severe Hypoxic Respiratory Failure Research Articles

Prone Positioning in Mechanically Ventilated COVID-19 Patients: Timing of Initiation and Outcomes

The COVID-19 pandemic led to a broad implementation of proning to enhance oxygenation in both self-ventilating and mechanically ventilated critically ill patients with acute severe hypoxic respiratory failure. However, there is little data on the impact of the timing of the initiation of prone positioning in COVID-19 patients receiving mechanical ventilation. In this study, we analyzed our proning practices in mechanically ventilated COVID-19 patients. There were 931 total proning episodes in 144 patients, with a median duration of 16 h (IQR 15–17 h) per proning cycle. 563 proning cycles were initiated within 7 days of intubation (early), 235 within 7–14 days (intermediate), and 133 after 14 days (late). The mean change in oxygenation defined as the delta PaO2/FiO2 ratio (ΔPF) after the prone episode was 16.6 ± 34.4 mmHg (p < 0.001). For early, intermediate, and late cycles, mean ΔPF ratios were 18.5 ± 36.7 mmHg, 13.2 ± 30.4 mmHg, and 14.8 ± 30.5 mmHg, with no significant difference in response between early, intermediate, and late proning (p = 0.2), respectively. Our findings indicate a favorable oxygenation response to proning episodes at all time points, even after >14 days of intubation. However, the findings cannot be translated directly into a survival advantage, and more research is needed in this area.

Wine-processed radix scutellariae alleviates ARDS by regulating tryptophan metabolism through gut microbiota.

Acute respiratory distress syndrome (ARDS) is an acute and diffuse pulmonary inflammation, characterized by severe hypoxic respiratory failure caused by inflammatory tissue damage, which is a common cause of respiratory failure. Currently, there is no treatment available that can prevent or reverse the devastating effects caused by these conditions. The purpose of this study was to determine the effects of WRS on gut microbiota and the potential effect of gut microbiota on the treatment of lung disease by using a staphylococcal enterotoxin B (SEB)-induced ARDS model. The results showed that WRS could significantly reduce the pathological damage to lung and colon tissues and improve the lung and intestinal functions of ARDS mice. WRS was able to improve the level of cytokines in serum and lung tissue. Additionally, WRS could reverse the gut microbiota dysbiosis caused by SEB in ARDS mice. WRS increases the production of short-chain fatty acids (SCFAs) in the gut. This increase in SCFAs may lead to increased migration of SCFAs to the lungs and activation of free fatty acid receptors (FFAR) three and FFAR2 in lung epithelial cells, alleviating the symptoms of ARDS. Interestingly, WRS improves the faecal metabolite profiles in SEB-induced ARDS mice via tryptophan metabolism. On the basis of the component-target-metabolism strategy, baicalin, oroxylin A-7-O-glucuronide and skullcapflavon II were identified as the potential bioactive markers in WRS for the treatment of ARDS. Our study showed that WRS could ameliorate SEB-induced ARDS by regulating the structure of gut microbiota, increasing the production of SCFAs and modifying the faecal metabolite profiles through the lung-gut axis, and providing alternative treatment strategies for lung disease.

What did we learn about coronavirus disease-19-associated acute kidney injury during the pandemic?

Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

Detailed Analysis of Primary Non-invasive Respiratory Support and Outcomes of Subjects With COVID-19 Acute Hypoxaemic Respiratory Failure.

Background The role of non-invasive (continuous positive airway pressure (CPAP) or Non-invasive ventilation (NIV)) respiratory support (NIRS) as a primary oxygenation strategy for COVID-19 patients with acute severe hypoxic respiratory failure (AHRF), as opposed to invasive mechanical ventilation (invasive-MV), is uncertain. While NIRS may prevent complications related to invasive MV, prolonged NIRS and delays in intubation may lead to adverse outcomes. This study was conducted to assess the role of NIRS in COVID-19 hypoxemic respiratory failure and to explore the variables associated with NRIS failure. Methods This is a single-center, observational study of two distinct waves of severe COVID-19 patients admitted to the ICU. Patients initially managed with non-invasive respiratory support with laboratory-confirmed SARS-CoV-2 in acute hypoxaemic respiratory failure were included. Demographics, comorbidities, admission laboratory variables, and ICU admission scores were extracted from electronic health records. Univariate and multiple logistic regression was used to identify predictive factors for invasive mechanical ventilation. Kaplan-Meier survival curves were used to summarise survival between the ventilatory and time-to-intubation groups. Results There were 291 patients, of which 232 were managed with NIRS as an initial ventilation strategy. There was a high incidence of failure (48.7%). Admission APACHE II score, SOFA score, HACOR score, ROX index, and PaO2/FiO2 were all predictive of NIRS failure. Daily (days 1-4) HACOR scores and ROX index measurements highly predicted NIRS failure. Late NIRS failure (>24 hours) was independently associated with increased mortality (44%). Conclusion NIRS is effective as first-line therapy for COVID-19 patients with AHRF. However, failure, particularly delayed failure, is associated with significant mortality. Early prediction of NIRS failure may prevent adverse outcomes.

Managing Severe Hypoxic Respiratory Failure in COVID-19.

Purpose of ReviewAdult respiratory distress syndrome is a life-threatening complication from severe COVID-19 infection resulting in severe hypoxic respiratory failure. Strategies at improving oxygenation have evolved over the course of the pandemic.Recent FindingsAlthough non-invasive respiratory support reduces the need for intubation, a significant number of patients with COVID-19 progress to invasive mechanical ventilation. Once intubated, a lung protective ventilation strategy should be employed that limits tidal volumes to 6 ml/kg of predicted body weight and employs sufficient positive end-expiratory pressure to maximize oxygen delivery while minimizing the fraction of inspired oxygen. Intermittent prone positioning is effective at improving survival, and there is a growing body of evidence that it can be safely performed in spontaneously breathing patients to reduce the need for invasive mechanical ventilation. Inhaled pulmonary vasodilators have not been shown to improve survival or cost-effectiveness in COVID-19 and should be used selectively.SummaryFinally, the best outcomes are likely achieved at centers with experience at severe ARDS management and protocols for escalation of care.

Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19.

BackgroundThere have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support.MethodsProspectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient.ResultsFifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. −4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26).ConclusionsThe response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

Abstract P5-18-03: Hepatopulmonary syndrome with long term use of ado-trastuzumab emtansine (T-DM1)

Abstract Introduction: Hepatopulmonary syndrome (HPS) is characterized by hypoxemia, portal hypertension, and intrapulmonary shunting and manifests as dyspnea. The portal hypertension may be a result of cirrhosis or non-cirrhotic causes such as nodular regenerative hyperplasia of the liver that is associated with drug therapy. Progressive hypoxemia often occurs despite stable liver function. Ado-trastuzumab emtansine (T-DM1; KADCYLA) is an antibody-drug conjugate comprised of a humanized monoclonal antibody trastuzumab covalently linked to the cytotoxic agent maytansine. T-DM1 is prescribed in the postneoadjuvant setting in persons with residual invasive HER2-positive (HER2+) breast cancer (BC) as well as in persons with metastatic HER2+ BC who were previously treated with trastuzumab and a taxane. Liver toxicities including an asymptomatic, transient increase in transaminases and nodular regenerative hyperplasia that results in portal hypertension have been described; however, HPS secondary to noncirrhotic portal hypertension occurring with long-term exposure to T-DM1 has not been reported. We have identified patients (pts) with this infrequent, yet serious complication, and we aim to better characterize their clinical course to guide earlier detection and hopefully prevent irreversible hypoxic respiratory failure. Methods: Institutional search tools were utilized to identify pts at Mayo Clinic with HER2+ BC treated with T-DM1 in either the postneoadjuvant or metastatic setting. Electronic health records were manually reviewed for HPS criteria including 1) hypoxemia 2) portal hypertension and 3) intrapulmonary shunt/vasodilation confirmed by contrast echocardiogram or macroaggregated albumin lung perfusion scan. For pts meeting criteria for HPS, imaging was independently reviewed by a hepatologist to determine whether there was preexisting liver disease or if changes occurred after initiation of T-DM1. Results: We identified 259 pts with HER2+ BC treated with T-DM1 in the postneoadjuvant (n=70) or metastatic setting (n=185). Four pts met criteria for HPS (1.5%) while receiving T-DM1 for metastatic disease (Table 1; listed in chronological order of onset of HPS). Median age was 43 (range 35 - 53 years), median prior lines of treatment was 1.5 (range 0 - 7), and the median number of cycles of T-DM1 prior to discontinuation was 68.5 (range 51 - 90). All pts had evidence of left atrial enlargement on echocardiogram, and evidence of portal hypertension as determined by the presence of varices, and splenomegaly. Three pts had documented telangiectasias as well as Grade 1-2 elevations in serum transaminases and bilirubin. Elevations in hemoglobin were noted in 2 pts during treatment with T-DM1. All pts had a confirmed intrapulmonary shunt via contrast echocardiogram and a lung perfusion scan. Three pts discontinued T-DM1 after diagnosis of HPS and experienced some clinical improvement in hypoxia. One pt died two months after stopping T-DM1 due to progression of BC. Conclusion: HPS may occur in the setting of prolonged exposure to T-DM1 and can be associated with severe hypoxic respiratory failure. Further data are required to characterize the spectrum of liver injury that occurs with long-term use of T-DM1 to provide further guidance to clinicians as regards monitoring for these adverse effects. Patients who developed hepatopulmonary syndrome while on T-DM1Age, yrsSites of metastases# lines of prior txCycles of T-DM1Presenting sign or symptomsNon-contrast ECHO findingsSupplemental oxygenTransaminitis; hyperbilirubinemiaEvidence of portal hypertensionTelangiectasiasHgb prior to T-DM1Hgb end of txLung perfusion studyContrast ECHOPt 153LN, bone090DOE, hypoxemia, clubbingleft atrial enlargement (62 mg/m2)YesNovarices, splenomegalyNot documented12.9 g/dL10.7 g/dL13.5%Yes, small shuntPt 235LN, bone, liver751DOEleft atrial enlargement (54 mg/m2)YesGrade 1; Grade 2varices, splenomegaly; thrombocytopeniaYes, face and handsn/a11.9 g/dL24%Yes, large shuntPt 338LN, bone251Hyperbilirubinemiaborderline left atrial enlargementYesGrade 1; Grade 2varices, splenomegalyYes, trunk, extremities, face11.7 g/dL16.2 g/dL17.8%Yes, moderate shuntPt 448LN, liver186DOEleft atrial enlargement (49 mg/m2)NoGrade 1; Grade 2varices, splenomegalyYes, trunk12.5 g/dL16.1 g/dL7.9%Yes, large shunt Citation Format: Ally Higgins, Adham K Alkurashi, Patrick S Kamath, Vivek N Iyer, Ciara O'Sullivan, Tufia C Haddad. Hepatopulmonary syndrome with long term use of ado-trastuzumab emtansine (T-DM1) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-03.

COVID-19 in a mosaic trisomy 13 patient with polycystic kidney disease

Presentation, management, and outcomes of COVID-19 infections among younger patients is an area of medicine with deficits in research, likely due to the lower incidence of severe COVID-19 disease among the younger population. Management can be challenging, and clinicians often guide their decision-making based on the ever-changing protocols that are tailored mostly to the elderly population. Even more underrepresented in COVID-19 research are patients with chromosomal abnormalities and trisomy syndromes, as they appear less frequently, but have risk of increased morbidity and mortality due to underlying medical conditions. We describe a case of severe COVID-19 infection in a young patient with mosaic trisomy 13 and pre-existing polycystic kidney disease, who developed severe acute hypoxic respiratory failure and acute chronic kidney injury. The patient was provided maximal pharmacological support and her clinical course helps to shape the understanding of COVID-19 infections in the setting of chromosomal abnormalities and complex medical history.

Inhaled Nitric Oxide Therapy for Pulmonary Arterial Hypertension of Newborn

Background: Inhaled nitric oxide (iNO) has been in use for several decades now in neonates with hypoxic respiratory failure (HRF) associated with pulmonary hypertension (PH). Its requirement is uncommon, and is considered as an advanced form of support that is not widely available. Analysis of outcomes in specific settings, notably from low-middle income countries, is crucial. Objectives: To evaluate the patient profile and outcomes of neonates treated with iNO in our Level IIIB unit. Methods: This retrospective observational study describes the clinical diagnosis, management strategies and short-term outcomes of all neonates who received iNO in the years between 2013 and 2021. Details were retrieved from Electronic Medical Records and systematically analysed. Observation: Of 35 infants who received iNO during the study period, 31 (88.6%) were &gt;34 weeks. The median and interquartile range (IQR) of oxygenation index at which iNO was started was 28 (20,33). The median (IQR) duration of iNO therapy was 48 (23,95) hours. Overall, 18 neonates (51.4%) survived till hospital discharge. Therapeutic response was best observed in infants with HRF secondary to meconium aspiration syndrome or congenital pneumonia (100% survival). Though the benefits of iNO use in congenital diaphragmatic hernia and bronchopulmonary dysplasia associated with PH are debatable, its use continues as a rescue measure. Conclusion: iNO is used in severe HRF associated with PH in neonates and can improve survival rates in select patient profiles without any major adverse outcomes.

High Flow in the Storm. Early Administration of High-Flow Nasal Cannula in Patients with Severe Acute Hypoxic Respiratory Failure Due to Clinically Suspected COVID-19

Background: The worldwide COVID-19 pandemic has created a shortage of ICU beds and ventilators. The objective was to assess whether administration of high-flow nasal cannula (HFNC) in patients with acute hypoxic respiratory failure due to COVID-19 averted mechanical ventilation (MV). Methods: Prospective observational study performed at Hospital Universitario HM Puerta del Sur (Madrid). The protocol included early administration of HFNC in clinically suspected COVID-19 patients with progressive desaturation. Results: Twenty patients were started on respiratory support with HFNC. Hospital admission took place after a median of 7 days since symptom onset and clinical deterioration was apparent at 9 days after symptom onset. Anti-inflammatory treatment with methylprednisolone and tocilizumab was initiated at 9 days (6.5–12), followed by HFNC at 9.5 days (7–12). HFNC was maintained for an average of 4.5 days (2.8–6.3), was successful in eighteen patients (90%), as defined by not needing invasive MV, and failed in two cases (10%) resulting in death. Since HFNC was implemented, there has been a decrease in the number of patients admitted to the ICU and treated with MV for acute hypoxic respiratory failure. Conclusions: HFNC administration may represent a viable therapeutic option for patients in the early stages of severe respiratory failure due to clinically suspected COVID-19.

ANCHORING BIAS DURING THE COVID-19 PANDEMIC

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Patients presenting in New York City, the epicenter for COVID in the United States, with severe hypoxic respiratory failure in the past year with acute respiratory distress syndrome (ARDS) signs were thought to exclusively have COVID-19 pneumonia. Even if initial tests were negative, physicians often anchored on the diagnosis of COVID as the disease was rapidly spreading and hospitals were at maximum capacity. We present a case of a young male who presented with severe hypoxic respiratory failure in the early stages of the pandemic who was found to be negative for COVID-19 and subsequently found to have pneumocystis jiroveci pneumonia (PJP). CASE PRESENTATION: This is a 42 year-old male with a past medical history of controlled diabetes mellitus type 2, hypertension, and a previous smoker who presented with worsening progressive shortness of breath for three days. On admission, the patient was found to be tachycardic, tachypneic and hypoxic. Chest x-ray showed bilateral diffuse infiltrates most consistent with ARDS. ABG revealed severe hypoxia with PO2 of 39 on room air. He was initially placed on bi-level with minimal improvement and was subsequently intubated. Initial oropharyngeal and nasopharyngeal COVID-19 swabs were negative. His influenza PCR also resulted as negative. Sputum cultures, endotracheal aspirate and blood cultures all returned back negative. On day three of his admission, the patient was tested for HIV and found to be positive with CD4 count <50. He was started on TMP-SMX and methylprednisolone for suspected PJP pneumonia. Due to fears from the ongoing and heightening pandemic, the patient was tested yet again for COVID swab and it resulted negative. He underwent a bronchoscopy with BAL which confirmed the diagnosis of PJP. Patient continued to improve on antibiotics, was eventually extubated, and started on antiretroviral therapy with improvement of CD4 at three month follow-up. DISCUSSION: Physicians have become blinded from the COVID pandemic and often anchor to the diagnosis of severe hypoxic respiratory failure from COVID-19. Other diseases such as PJP can present similarly and prompt treatment is necessary. PJP has a high morbidity and mortality rate amongst immunocompromised patients and remains a leading opportunistic infection in AIDS patients. Our patient was a school teacher who denied any intravenous drug abuse or high-risk sexual encounters. CONCLUSIONS: Although many patients present with severe hypoxic respiratory distress and require mechanical ventilation during the ongoing COVID-19 pandemic, it is important to rule out other infectious causes of ARDS such as PJP which can also lead to morbid outcomes if not treated appropriately. REFERENCE #1: Gaborit BJ, Tessoulin B, Lavergne RA, et al. Outcome and prognostic factors of Pneumocystis jirovecii pneumonia in immunocompromised adults: a prospective observational study. Ann Intensive Care. 2019;9(1):131. Published 2019 Nov 27. doi:10.1186/s13613-019-0604-x REFERENCE #2: Harris, J.R., Balajee, S.A. & Park, B.J. Pneumocystis Jirovecii Pneumonia: Current Knowledge and Outstanding Public Health Issues. Curr Fungal Infect Rep 4, 229–237 (2010). https://doi.org/10.1007/s12281-010-0029-3 DISCLOSURES: No relevant relationships by Sahar Ilyas, source=Web Response No relevant relationships by Navim Mobin, source=Web Response No relevant relationships by Nisha Patel, source=Web Response No relevant relationships by Michal Tokarski, source=Web Response

30-DAY AND 90-DAY OUTCOMES OF THE SURVIVORS OF COVID-19 PNEUMONIA TREATED EXCLUSIVELY WITH CPAP: RESULTS FROM A DISTRICT TEACHING HOSPITAL

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: The recent two waves of the pandemic have caused over 127,000 deaths in the UK, with over 4.4 million cases and estimated global mortality of approximately 3 million when writing this abstract. Patients hospitalised with COVID-19 pneumonia have severe hypoxic respiratory failure, and it can be challenging to maintain adequate oxygenation with traditional oxygen supplementation. Continuous Positive Airway Pressure (CPAP) was used to avoid mechanical ventilation and rationalise oxygen stocks. CPAP is beneficial in studies globally. We studied the outcomes of the survivors of COVID 19 pneumonia treated exclusively with CPAP who belonged to the Not for ICU group, admitted exclusively to the ward-based CPAP unit. METHODS: Retrospective data were collected on the survivors of patients admitted to a ward-based CPAP in Suspected or confirmed COVID-19 with pneumonitis and type 1 Respiratory failure. Patients admitted for BIPAP were excluded. Patients on CPAP for OSA or Obesity Hypoventilation syndrome who required being in the unit for infection control purposes were also excluded. Data collected on basic demographics and specific information like comorbidities, status length of stay, CPAP duration, discharge prescription of oxygen were collected and analysed. RESULTS: 28 patients were identified who received CPAP only during both the first and second wave (March to July 2021 and January to March 2021) of the pandemic. 17 Males and 11 females, 60% and 40% respectively, received CPAP only—the average age was 63.5 years, range 37 to 86 years. Twenty-six out of survivors of CPAP only treatment group 28 are alive, at 30 days 60 days and 26 were alive at 90 days. The mean length of stay of this cohort was 23 days due to rehabilitation requirements. Further, twenty-seven out of twenty-eight patients (96% ) were COVID PCR positive, and one patient was COVID PCR negative but radiology consistent with COVID pneumonitis. Nine patients (31.2%) were discharged on home oxygen;4 of them had a respiratory morbidity -2 patients with ILD, two patients with COPD. At 90 days, 4 of these nine patients discharged on home oxygen were still on oxygen Duration CPAP ranged from and 3 to 14 days with an average of 6.33 days. Two patients were on CPAP at discharge due to a new diagnosis of Obesity hypoventilation /OSA, and 5 of them were on CPAP for OSA at admission. The most common comorbidities among this cohort were Hypertension 9/28, Diabetes mellitus 7/28, Asthma 4/28 and COPD 3 /28 patients CONCLUSIONS: Patients treated who received exclusive ward-based CPAP due to being not for ICU level of care had a good 60-day 90-day survival. Up to a third (31.2%) were still requiring oxygen at the time of discharge, indicating a prolonged recovery phase of the respiratory failure.15% still on oxygen at 90 days. CLINICAL IMPLICATIONS: CPAP for COVID pneumonia has favourable outcome even at 60 and 90 days post CPAP, with a third of patients requiring oxygen at discharge. DISCLOSURES: No relevant relationships by Wee Teck Lim, source=Web Response No relevant relationships by Farah Asyikin Mohamad Nasir, source=Web Response No relevant relationships by Ernest Okpo, source=Web Response No relevant relationships by Aravind Ponnuswamy, source=Web Response No relevant relationships by Tariq Trussell, source=Web Response

IS ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA AN EMERGING CAUSE OF DIFFUSE ALVEOLAR HEMORRHAGE?

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare and poorly understood form of interstitial lung disease that can present either acutely or insidiously. Among the acute manifestations of AFOP, diffuse alveolar hemorrhage (DAH) has only been described once before in the literature. CASE PRESENTATION: A 25 year old male with a history of end stage renal disease secondary to bilateral posterior urethral valves (on hemodialysis) and cutaneous neutrophilic dermatosis (Sweet syndrome) presented with the abrupt onset of severe dyspnea. Given concern for flash pulmonary edema on initial chest radiograph (Figure 1), he was placed on a nitroglycerine drip and underwent emergent hemodialysis with ultrafiltration. He subsequently developed rapidly progressive acute hypoxic respiratory failure with worsening pulmonary infiltrates (Figure 2) requiring emergent intubation and mechanical ventilation. Copious bloody secretions were noted during intubation, and the patient required multiple blood transfusions following admission. Despite mechanical ventilation with paralysis and proning, the patient developed severe adult respiratory distress syndrome with a P:F ratio nadir of 74. Chest CT revealed diffuse severe consolidative lung injury of unclear etiology (Figure 3). Bronchoscopy with serial aliquots on bronchoalveolar lavage confirmed the presence of diffuse alveolar hemorrhage. The patient’s condition improved rapidly with initiation of systemic glucocorticoids, and he was subsequently extubated on hospital day 5. Shortly after discharge home, the patient was readmitted with recurrent severe acute hypoxic respiratory failure in the setting of tapering his glucocorticoids, but he was successfully extubated within 24 hours following reinitiation of high-dose systemic glucocorticoids. Bronchoscopically-guided cryobiopsy during this admission revealed a diagnosis of AFOP, and the patient was ultimately discharged home with plans for a prolonged course of steroids and possible transition to steroid-sparing agents. DISCUSSION: Further investigations are needed to determine whether AFOP represents a distinct clinical entity, or rather the sequelae of concomitant inflammatory or autoimmune processes such as those present in this patient. Regardless of the etiology, data from case reports suggest that AFOP can be highly responsive to systemic glucocorticoids and other forms of immunosuppression. Delay in diagnosis, however, remains a significant barrier to the treatment of AFOP and portends poor prognosis in the acute form of this illness. CONCLUSIONS: The addition of this case to the literature suggests that DAH may represent an emerging manifestation of AFOP. Prompt recognition of this rare and heterogeneous disease process is imperative, as increasing evidence suggests favorable outcomes with early initiation of systemic glucocorticoids. REFERENCE #1: Crowley N, Sessler C, Miller K, Robila V, Debesa, O. Relapsing acute fibrinous and organizing pneumonia complicated by diffuse alveolar hemorrhage. Chest. 2018;154(4)(suppl):409A-410A. doi: 10.1016/j.chest.2018.08.375. REFERENCE #2: Lee JH, Yum HK, Jamous F, Santos C, Campisi A, Surani S, Lococo F, Goo JM, Yoon SH. Diagnostic procedures and clinico-radiological findings of acute fibrinous and organizing pneumonia: a systematic review and pooled analysis. Eur Radiol. 2021 Mar 31. doi: 10.1007/s00330-021-07868-z. Epub ahead of print. REFERENCE #3: Santos C, Oliveira RC, Serra P, Baptista JP, Sousa E, Casanova P, Pimentel J, Carvalho L. Pathophysiology of acute fibrinous and organizing pneumonia - Clinical and morphological spectra. Pathophysiology. 2019 Sep-Dec;26(3-4):213-217. doi: 10.1016/j.pathophys.2019.04.001. DISCLOSURES: No relevant relationships by Andrew Davis, source=Web Response No relevant relationships by Nathan Sandbo, source=Web Response

SEVERE NONINFECTIOUS PNEUMONITIS ASSOCIATED WITH IBRUTINIB FOR DIFFUSE LARGE-B-CELL LYMPHOMA

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Ibrutinib is an oral Bruton's tyrosine kinase inhibitor that is indicated in treatment of certain lymphomas and is now being investigated for primary CNS diffuse large B-cell lymphoma (DLBCL). We present a case of severe non-infectious pneumonitis in a patient receiving ibrutinib for recurrent primary CNS DLBCL CASE PRESENTATION: A 51-year-old male with primary CNS DLBCL was treated with ibrutinib in a clinical trial after failure of first line and salvage therapies. Seven weeks after initiation of the drug, patient presented with dyspnea, tachypnea, tachycardia, and encephalopathy to the hospital. Shortly after admission, patient developed worsening hypoxia and encephalopathy requiring intubation and mechanical ventilation. Labs demonstrated mild anemia and elevated LDH without leukocytosis or thrombocytopenia. Blood cultures and nasopharyngeal PCR for SARS-CoV-2 were negative. CT chest showed non-specific upper lung predominant extensive bilateral ground glass opacities with patchy consolidation. Differential diagnosis included infectious and inflammatory etiologies. Bronchoalveolar lavage was negative for viral, mycobacterial, fungal or bacterial pathogens. Ibrutinib was discontinued and patient was treated with 60 mg intravenous methylprednisolone daily. Patient's was successfully extubated with resolving hypoxia. DISCUSSION: Common adverse effects from treatment with ibrutinib include diarrhea, hypertension, fatigue, infections, and atrial fibrillation. Although infectious pneumonias have been documented, only a few accounts of non-infectious pneumonitis have been reported in the extant medical literature. Both non-specific interstitial pneumonia and organizing pneumonia cases have been reported. Early recognition in appropriate clinical context, discontinuation of offending drug, and treatment with steroids is warranted. CONCLUSIONS: Patients on targeted therapy with Ibrutinib are at risk of developing severe hypoxic respiratory failure from non-infectious pneumonitis. Timely consideration, treatment with steroids and ventilatory support can help with recovery. REFERENCE #1: 1. Mato AR, Islam P, Daniel C, Strelec L, Kaye AH, Brooks S, et al. Ibrutinib-induced pneumonitis in patients with chronic lymphocytic leukemia. Blood. 2016;127(8):1064-7. REFERENCE #2: 2. Murthy V, Suh J, Bradshaw A-d, Sloance M. Ibrutinib-Induced Rapidly Progressive Inflammatory Pneumonitis. C51 TOXIC INGESTIONS AND EXPOSURES. p. A4584-A. REFERENCE #3: 3. Blackwell L, Cai D, Srinivas S, Lovoulos C, Kim J. Ibrutinib-Induced Organizing Pneumonia. CHEST. 2016;150(4):782A. DISCLOSURES: No relevant relationships by zainub ajmal, source=Web Response No relevant relationships by Gowthami Kobbari, source=Web Response No relevant relationships by Fatima Tuz Zahra, source=Web Response No relevant relationships by Gregory Wu, source=Web Response

Clinical Profile and Predictors of Mortality in Neonates Born With Non-Immune Hydrops Fetalis: Experience From a Lower-Middle-Income Country.

IntroductionHydrops fetalis (HF) is a life-threatening condition in which a fetus has an abnormal collection of fluid in the tissue around the lungs, heart, abdomen, or under the skin. Based on its pathophysiology, it is classified into immune and non-immune types. With the widespread use of anti-D immunoglobulin, non-immune HF has become more common, with an incidence of one in 1,700-3,000 live births. A multitude of fetal diseases with various causes can lead to non-immune HF. Due to the recent advances in prenatal diagnostic and therapeutic interventions together with improved neonatal intensive care, the diagnosis and subsequent management of HF have been refined. However, HF is still associated with a high mortality rate. A recent assessment of the literature found that there is a lack of data on prognostic variables in neonates with HF from low- and middle-income countries. In light of this, we sought to establish the etiologic causes, predictors of mortality, and eventual fate of newborns born non-immune HF at the Aga Khan University Hospital, Karachi during the 10-year period spanning January 2009-December 2019 in this retrospective analysis.MethodologyFor this study, we collected data from the computerized database and patient record files at the hospital on all infants with non-immune HF. Demographic data, postnatal interventions, clinical and laboratory findings, outcomes, and the results of comparison between HF patients who died and those who survived were analyzed.ResultsThe incidence of non-immune HF at our hospital was 0.62/1,000 live births during the period under study, with 33 newborn babies diagnosed with non-immune HF from a total of 53,033 live-born deliveries. An etiologic factor was discovered in 17 (51.5%) neonates with non-immune HF while 16 (48.4%) were classified as those with unidentified etiology. The most common causes were cardiovascular and genetic syndromes, which resulted in 100% mortality. The overall mortality rate was 67%. The need for mechanical ventilation, surfactant therapy, and prolonged hospitalization were identified as independent risk factors of mortality.ConclusionOur study proves that the need for mechanical ventilation [moderate to severe hypoxic respiratory failure (HRF)] and prolonged hospitalization are strong predictors of poor outcomes in neonates with non-immune HF. Therefore, severe hydrops causing significant mortality can be anticipated based on the patients' respiratory status and the need for escalated oxygen support.

Complete Heart Block as a Clinical Feature in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series of Three Cases

Background. Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. However, there have been very few reports on complete heart block (CHB) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of critically ill COVID-19 patients complicated by CHB. Case Summary. We present three cases of new-onset CHB in critically ill COVID-19 patients. Patient 1 is a 41-year-old male with well-documented history of Familial Mediterranean Fever (FMF) who required mechanical ventilator support for acute hypoxic respiratory failure from severe COVID-19 pneumonia. He developed new-onset CHB without a hemodynamic derangement but subsequently had acute coronary syndrome complicated by cardiogenic shock. Patient 2 is a 77-year-old male with no past medical history who required intubation for severe COVID-19 pneumonia acute hypoxic respiratory failure. He developed CHB with sinus pause requiring temporary pacing but subsequently developed multiorgan failure. Patient 3 is 36-year-old lady 38 + 2 weeks pregnant, gravida 2 para 1 with no other medical history, who had an emergency Lower Section Caesarean Section (LSCS) as she required intubation for acute hypoxic respiratory failure. She exhibited new-onset CHB without hemodynamic compromise. The CHB resolved spontaneously after 24 hours. Discussion. COVID-19-associated CHB is a very rare clinical manifestation. The potential mechanisms for CHB in patients with COVID-19 include myocardial inflammation or direct viral infiltration as well as other causes such as metabolic derangements or use of sedatives. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and hemodynamic instability.

Predictive Role of Haematological Determinants on Outcomes of Critically Ill COVID-19 Patients Admitted to Intensive Care Unit.

Background: The mortality of patients admitted to the intensive care unit (ICU) with COVID-19 remains significantly high. Severe COVID-19 pneumonia is characterised by refractory hypoxemia with significant shunting due to a combination of alveolar damage, vascular vasoconstriction, and occlusion due to microthrombi. Similar pathological features are seen in extra-pulmonary organs. However, the influence of thrombotic markers on the risk of mechanical ventilation (MV) and the development of acute kidney injury (AKI) is not fully defined.Methods: This was a cross-sectional evaluation of haemostatic and thrombotic markers of COVID-19 patients admitted to the ICU to determine their predictability for the development of thromboembolism and the need for non-invasive or invasive MV, development of AKI, and mortality.Results: An extended coagulation profile was obtained in 71 SARS-CoV-2 positive patients admitted to the ICU. All patients had acute severe hypoxic respiratory failure and required non-invasive or invasive MV. There were increases in peak D-dimer (3.0 mg/L), factor VIII levels (255 IU/dL) vWF antigen (471 IU/dL) with low ADAMTS13 activity (54.7 IU/dL) compared to the reference ranges. Peak D-dimer was consistently raised in patients who developed AKI and required invasive MV. ADAMTS13/vWF/platelet axis was associated with disease severity, multi-organ dysfunction, and mortality.Conclusions: Haematological abnormalities are a common feature of severe COVID-19 pneumonia. We found peak D-dimer and vWF-ADAMTS13-platelet axis are associated with increased ICU severity and outcome in severe COVID-19 patients admitted to ICU. Larger studies are needed to evaluate this more comprehensively.

Loculated Empyema and SARS-CoV-2 Infection: A Report of Two Cases and Review of the Literature.

The clinical manifestations of COVID-19 vary from mild to severe disease and can result in multi-organ failure.Pleural empyema is usually treated with a combination of antibiotics and surgical drainage of the pleural cavity.

Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk.

BackgroundSevere hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven.ObjectivesThe primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure.MethodsA multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit.ResultsThe steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection.Conclusion and RelevanceCombination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

Defining COVID-19-associated hyperinflammatory syndrome in specific populations.

Defining COVID-19-associated hyperinflammatory syndrome in specific populations.