Outcomes of extracorporeal membrane oxygenation in immunosuppressed vs. Immunocompetent patients.

INTRODUCTION: Immunosuppressed hosts represent a growing group of patients who suffer acute respiratory failure and may be considered for therapies such as extracorporeal membrane oxygenation (ECMO). OBJECTIVES: We conducted this retrospective study to determine whether acutely or chronically immunosuppressed patients placed on ECMO for cardiac and/or respiratory failure in our institution have different outcomes than immunocompetent patients placed on ECMO in our institution. METHODS: Adult patients placed on ECMO between June 31, 2010 and July 7, 2021 were identified within an IRB-approved database. Data was retrospectively extracted from the database and patients' medical records. Patients who survived ECMO decannulation were sub-grouped by the presence of acute or chronic immunosuppression, defined by the use of high-dose steroids or immunosuppressive agents for greater than four weeks prior to ECMO initiation. We analyzed and compared baseline characteristics and clinical outcomes using chi-squared tests for categorical variables and a one-way analysis of variance (ANOVA) for continuous variables. RESULTS: 385 patients were included in this study, with 39 identified as chronically immunosuppressed, 49 as acutely immunosuppressed, and 297 as immunocompetent. There was no statistical difference in ECMO survival (respectively 54%, 59%, 65% p = 0.359) or 30-day survival (33%, 51%, 48% p = 0.149) for chronically immunosuppressed, acutely immunosuppressed, and immunocompetent, respectively. There were significant differences in rates of pre-ECMO COVID infection (p<0.001), coronary artery disease (p<0.001), smoking (p = 0.003), and acute kidney injury (p = 0.032). Acutely immunosuppressed patients had the highest rates of new infections during ECMO (p = 0.006). CONCLUSION: When compared to immunocompetent patients, both acutely and chronically immunosuppressed patients had no significant difference in ECMO survival or 30-day survival. Acutely immunosuppressed patients had less comorbidities than chronically immunosuppressed patients, but they were more commonly infected during ECMO. ECMO may still be a valuable tool in appropriately selected patients with refractory respiratory or cardiac failure.

A multidisciplinary approach to prolonged extracorporeal membrane oxygenation for acute respiratory distress syndrome due to coronavirus 2019-case report.

Patients with novel coronavirus 2019 (COVID-19) may develop acute respiratory distress syndrome (ARDS) and require extracorporeal membrane oxygenation (ECMO) support. Currently there is no specific treatment for COVID-19 available; thus, for patients with severe ARDS, the respiratory condition needs to improve while on ECMO support. Here we present a multidisciplinary team approach to the care of a patient with COVID-related ARDS requiring three months of veno-venous (VV) ECMO which lead to recovery. A 35-year-old male was transferred to us with ARDS due to COVID-19 infection with a lactate 13.7 mmol/L and an arterial-blood gas oxygenation of 75 mmHg on maximum ventilator settings. He was placed on VV ECMO during which he developed pneumonia, bacteremia, and pneumothoraces; however, his other organ functions were preserved. During his time in the Intensive Care Unit (ICU), multiple subspecialist teams participated in his care including physicians, pharmacists, nurses, nutritionists, case management, and social work. The VV ECMO was weaned off after 91 days of support, after which he had a prolonged hospital course due to inflammatory bowel disease, and aspiration pneumonia. CT scan performed six weeks prior to discharge showed mild improvement in diffuse airspace opacities superimposed on extensive chronic cystic changes. He was eventually discharged to a rehabilitation facility 68 days after ECMO removal. He was then seen in our outpatient pulmonary clinic one month and our Post-Intensive Care Syndrome clinic three months after discharge on two liters of nasal cannula oxygen. Pulmonary function testing done at this time demonstrated severe restrictive lung disease and severely reduced diffusion capacity. This case highlights the need for multidisciplinary collaboration among hospital teams to ensure success and patient survival in the setting of COVID ARDS. In those COVID ARDS patients with intact renal, metabolic, hematologic, and cardiovascular function, ECMO should be strongly considered.

Outcomes of extracorporeal membrane oxygenation in influenza versus COVID-19 during the first wave of COVID-19.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a refractory treatment for acute respiratory distress syndrome (ARDS) due to influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also referred to as coronavirus disease 2019 [COVID-19]). We conducted this study to compare the outcomes of influenza patients treated with veno-venous-ECMO (VV-ECMO) to COVID-19 patients treated with VV-ECMO, during the first wave of COVID-19. METHODS: Patients in our institution with ARDS due to COVID-19 or influenza who were placed on ECMO between August 1, 2010 and September 15, 2020 were included in this comparative, retrospective study. To improve homogeneity, only VV-ECMO patients were analyzed. The clinical characteristics and outcomes were extracted and analyzed. RESULTS: A total of 28 COVID-19 patients and 17 influenza patients were identified and included. ECMO survival rates were 68% (19/28) in COVID-19 patients and 94% (16/17) in influenza patients (p = .04). Thirty days survival rates after ECMO decannulation were 54% (15/28) in COVID-19 patients and 76% (13/17) in influenza patients (p = .13). COVID-19 patients spent a longer time on ECMO compared to flu patients (21 vs. 12 days; p = .025), and more COVID-19 patients (26/28 vs. 2/17) were on immunomodulatory therapy before ECMO initiation (p < .001). COVID-19 patients had higher rates of new infections during ECMO (50% vs. 18%; p = .03) and bacterial pneumonia (36% vs. 6%; p = .024). CONCLUSIONS: COVID-19 patients who were treated in our institution with VV-ECMO had statistically lower ECMO survival rates than influenza patients. It is possible that COVID-19 immunomodulation therapies may increase the risk of other superimposed infections.

COVID-19 treatment combinations and associations with mortality in a large multi-site healthcare system.

INTRODUCTION: During the early months of the COVID-19 pandemic, mortality associated with the disease declined in the United States. The standard of care for pharmacological interventions evolved during this period as new and repurposed treatments were used alone and in combination. Though these medications have been studied individually, data are limited regarding the relative impact of different medication combinations. The objectives of this study were to evaluate the association of COVID-19-related mortality and observed medication combinations and to determine whether changes in medication-related practice patterns and measured patient characteristics, alone, explain the decline in mortality seen early in the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted at a multi-hospital healthcare system exploring the association of mortality and combinations of remdesivir, corticosteroids, anticoagulants, tocilizumab, and hydroxychloroquine. Multivariable logistic regression was used to identify predictors of mortality for both the overall population and the population stratified by intensive care and non-intensive care unit admissions. A separate model was created to control for the change in unmeasured variables over time. RESULTS: For all patients, four treatment combinations were associated with lower mortality: Anticoagulation Only (OR 0.24, p < 0.0001), Anticoagulation and Remdesivir (OR 0.25, p = 0.0031), Anticoagulation and Corticosteroids (OR 0.53, p = 0.0263), and Anticoagulation, Corticosteroids and Remdesivir (OR 0.42, p = 0.026). For non-intensive care unit patients, the same combinations were significantly associated with lower mortality. For patients admitted to the intensive care unit, Anticoagulation Only was the sole treatment category associated with decreased mortality. When adjusted for demographics, clinical characteristics, and all treatment combinations there was an absolute decrease in the mortality rate by 2.5% between early and late periods of the study. However, when including an additional control for changes in unmeasured variables overtime, the absolute mortality rate decreased by 5.4%. CONCLUSIONS: This study found that anticoagulation was the most significant treatment for the reduction of COVID-related mortality. Anticoagulation Only was the sole treatment category associated with a significant decrease in mortality for both intensive care and non-intensive care patients. Treatment combinations that additionally included corticosteroids and/or remdesivir were also associated with decreased mortality, though only in the non-intensive care stratum. Further, we found that factors other than measured changes in demographics, clinical characteristics or pharmacological interventions accounted for an additional decrease in the COVID-19-related mortality rate over time.

Outcomes of extracorporeal membrane oxygenation in acute respiratory distress syndrome due to COVID-19: The lessons learned from the first wave of COVID-19.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) has been used as a refractory treatment for acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19), but there has been little evidence of its efficacy. We conducted this study to share our experience using ECMO as a bridge to recovery for ARDS due to COVID-19. METHODS: All adult patients who were placed on ECMO for ARDS due to COVID-19 between April 2020 and June 2020 (during the first wave of COVID-19) were identified. The clinical characteristics and outcomes of these patients were analyzed with a specific focus on the differences between patients who survived to hospital discharge and those who did not. RESULTS: In total, 20 COVID-19 patients were included in this study. All patients were placed on veno-veno ECMO. Comparing survivors and non-survivors, older age was found to be associated with hospital mortality (p = .02). The following complications were observed: renal failure requiring renal replacement therapy (35%, n = 7), bacteremia during ECMO (20%, n = 4), coinfection with bacterial pneumonia (15%, n = 3), cannula site bleeding (15%, n = 3), stroke (10%, n = 2), gastrointestinal bleeding (10%, n = 2), and liver failure (5%, n = 1). The complications associated with patient mortality were culture-positive septic shock (p = .01), culture-negative systemic inflammatory response syndrome (p = .01), and renal failure (p = .01). The causes of death were septic shock (44%, n = 4), culture-negative systemic inflammatory response syndrome (44%, n = 4), and stroke (11%, n = 1). CONCLUSIONS: Based on our experience, ECMO can improve refractory ARDS due to COVID-19 in select patients. Proper control of bacterial infections during COVID-19 immunomodulation therapy may be critical to improving survival.

Clinical presentations and outcomes in pulmonary embolism patients with cancer.

To study whether a diagnosis of cancer affects the clinical presentation and outcomes of patients with pulmonary embolism (PE). A retrospective analysis was performed of all consecutive patients diagnosed with PE on a computed tomography scan from 2014 to 2016 at an urban tertiary-referral medical center. Baseline characteristics, treatment decisions, and mortality data were compared between study subjects with and without a known diagnosis of active cancer. There were 581 subjects, of which 187 (33.0%) had a diagnosis of cancer. On average, cancer subjects tended to be older (64.8 vs. 58.5 years, p < 0.01), had lower body mass index (BMI) (29.0 vs. 31.5 kg/m2, p = 0.01), and were less likely to be active smokers (9.2% vs. 21.1%, p < 0.01), as compared to non-cancer subjects. Cancer subjects were also less likely to present with chest pain (18.2% vs. 37.4%, p < 0.01), syncope (2.7% vs. 6.6%, p = 0.05), bilateral PEs (50% vs. 60%, p = 0.025), and evidence of right heart strain (48% vs. 58%, p = 0.024). There was no difference in-hospital length of stay (8.9 vs. 9.4 days, p = 0.61) or rate of intensive care unit (ICU) admission (31.9% vs. 33.3%, p = 0.75) between the two groups. Presence of cancer increased the risk of all-cause one-year mortality (adjusted HR 9.7, 95% CI 4.8-19.7, p < 0.01); however, it did not independently affect in-hospital mortality (adjusted HR 2.9, 95% CI 0.86-9.87, p = 0.086). Patients with malignancy generally presented with less severe PE. In addition, malignancy did not independently increase the risk of in-hospital mortality among PE patients.

Utilization of extracorporeal life support for diffuse alveolar damage and diffuse alveolar hemorrhage: A systematic review.

Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.

Point-of-care versus central testing of hemoglobin during large volume blood transfusion.

BACKGROUND: Point-of-care (POC) hemoglobin testing has the potential to revolutionize massive transfusion strategies. No prior studies have compared POC and central laboratory testing of hemoglobin in patients undergoing massive transfusions. METHODS: We retrospectively compared the results of our point-of-care hemoglobin test (EPOC®) to our core laboratory complete blood count (CBC) hemoglobin test (Sysmex XE-5000™) in patients undergoing massive transfusion protocols (MTP) for hemorrhage. One hundred seventy paired samples from 90 patients for whom MTP was activated were collected at a single, tertiary care hospital between 10/2011 and 10/2017. Patients had both an EPOC® and CBC hemoglobin performed within 30 min of each other during the MTP. We assessed the accuracy of EPOC® hemoglobin testing using two variables: interchangeability and clinically significant differences from the CBC. The Clinical Laboratory Improvement Amendments (CLIA) proficiency testing criteria defined interchangeability for measurements. Clinically significant differences between the tests were defined by an expert panel. We examined whether these relationships changed as a function of the hemoglobin measured by the EPOC® and specific patient characteristics. RESULTS: Fifty one percent (86 of 170) of paired samples' hemoglobin results had an absolute difference of ≤7 and 73% (124 of 170) fell within ±1 g/dL of each other. The mean difference between EPOC® and CBC hemoglobin had a bias of - 0.268 g/dL (p = 0.002). When the EPOC® hemoglobin was < 7 g/dL, 30% of the hemoglobin values were within ±7, and 57% were within ±1 g/dL. When the measured EPOC® hemoglobin was ≥7 g/dL, 55% of the EPOC® and CBC hemoglobin values were within ±7, and 76% were within ±1 g/dL. EPOC® and CBC hemoglobin values that were within ±1 g/dL varied by patient population: 77% for cardiac surgery, 58% for general surgery, and 72% for non-surgical patients. CONCLUSIONS: The EPOC® device had minor negative bias, was not interchangeable with the CBC hemoglobin, and was less reliable when the EPOC® value was < 7 g/dL. Clinicians must consider speed versus accuracy, and should check a CBC within 30 min as confirmation when the EPOC® hemoglobin is < 7 g/dL until further prospective trials are performed in this population.

Utility of flexible bronchoscopy in the evaluation of pulmonary infiltrates in the hematopoietic stem cell transplant population -- a single center fourteen year experience.

INTRODUCTION: Pulmonary infiltrates are common within the hematopoietic stem cell transplant (HSCT) population and unfortunately portend an increased mortality. Bronchoscopy is often utilized as an initial diagnostic tool, but the literature supporting its diagnostic utility and effect on clinical management varies significantly. The aim of this study was to investigate the diagnostic ability, complication rate, and clinical impact of flexible bronchoscopy (FB) in evaluating pulmonary infiltrates in a large HSCT population. PATIENTS AND METHOD: Retrospective review of all patients undergoing FB after HSCT in the Bone Marrow Transplant Unit from 1996 to 2009. RESULTS: FB was performed 162times in 144patients with pulmonary infiltrates yielding positive results in 52.5%. The most common positive results were bacterial pneumonia (31%), fungal pneumonia (15%), and alveolar hemorrhage (11%). Treatment changes occurred in 44% of patients after FB. Treatment changes included antibiotic modification (59%), addition of corticosteroids (21%), antifungal modification (12%), and antiviral modification (7%). The overall complication rate associated with FB was 30%, although 84% of these complications were considered minor. CONCLUSIONS: FB in patients with pulmonary infiltrates after HSCT should still be considered a valuable tool in the evaluation and management of pulmonary infiltrates in the HSCT population. Future prospective, multicenter randomized studies are needed to evaluate the overall clinical impact that bronchoscopic results and management changes have in this unique population.

"Smoking wet": respiratory failure related to smoking tainted marijuana cigarettes.

Reports have suggested that the use of a dangerously tainted form of marijuana, referred to in the vernacular as "wet" or "fry," has increased. Marijuana cigarettes are dipped into or laced with other substances, typically formaldehyde, phencyclidine, or both. Inhaling smoke from these cigarettes can cause lung injuries. We report the cases of 2 young adults who presented at our hospital with respiratory failure soon after they had smoked "wet" marijuana cigarettes. In both patients, progressive hypoxemic respiratory failure necessitated rescue therapy with extracorporeal membrane oxygenation. After lengthy hospitalizations, both patients recovered with only mild pulmonary function abnormalities. To our knowledge, this is the first 2-patient report of severe respiratory failure and rescue therapy with extracorporeal oxygenation after the smoking of marijuana cigarettes thus tainted. We believe that, in young adults with an unexplained presentation of severe respiratory failure, the possibility of exposure to tainted marijuana cigarettes should be considered.

ACE inhibitor-induced angioedema.

Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials.

Use of mechanical ventilation and renal replacement therapy in critically ill hematopoietic stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is a treatment option for both malignant and nonmalignant disorders. HSCT patients remain at high risk for multiorgan failure, with previous studies noting mortality rates exceeding 90% when mechanical ventilation (MV) is required. We propose that advancements in critical care management and HSCT practices have improved these dismal outcomes. We performed a retrospective review of admissions to our bone marrow transplant unit between 2006 and 2010. All HSCT recipients requiring admission to the bone marrow transplant unit who received MV or renal replacement therapy (RRT) were evaluated. A total of 68 patients required MV. Twenty patients required RRT, all of whom required MV. Fifty-nine of the 68 ventilated patients died, for an overall mortality rate of 86.8%. The presence of renal failure and concomitant respiratory or liver dysfunction at the time of intubation was associated with a mortality rate of 100%. High mortality persists in our HSCT population requiring artificial support despite overall advances in critical care and HSCT practices. Critical care triage and management decisions in this high-risk population remain challenging.

What intensivists need to know about hemophagocytic syndrome: an underrecognized cause of death in adult intensive care units.

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a rare and frequently fatal disorder caused by an uncontrollable and ineffective systemic immune response. Patients initially present with fever, cytopenia, and hepatosplenomegaly, and subsequently develop multiorgan failure (MOF). Hemophagocytosis can be found on biopsy specimen but is not required. Acquired forms of HLH can occur in apparently healthy adults, while children present more often with an inherited form of the disease. Since HLH often presents with sepsis-like symptoms and organ dysfunction, patients are usually treated for presumed sepsis, which inevitably leads to delayed diagnosis and treatment. Intensivists need to have a low threshold for suspecting this disorder when previously healthy individuals present with a fulminant sepsis-like syndrome, which are unresponsive to conventional treatment. We present 3 patients with HLH who were admitted to our adult medical intensive care unit (MICU) over a 2-year period with fatal outcomes and emphasize the diagnostic importance of markedly elevated serum ferritin levels and the need for tissue biopsy in making an accurate diagnosis in a timely manner.

Thrombolytic therapy in a patient with suspected pulmonary embolism despite a negative computed tomography pulmonary angiogram.

We report a case of a 62-year-old male who presented to our intensive care unit with hypoxemia 6 hours after retinal surgery. He had a negative computed tomography (CT) pulmonary angiogram, but an emergency echocardiogram revealed the McConnell sign. He was thrombolysed and had rapid improvement in oxygenation and hemodynamics. Thrombolysis in hemodynamically unstable pulmonary embolism is not controversial, but most algorithms require confirmation of the diagnosis. Our patient had a negative CT pulmonary angiogram but was thrombolysed based on the clinical picture. Autopsy confirmed the diagnosis of multiple pulmonary emboli and unexpectedly discovered a patent foramen ovale that explained paradoxical embolism to the brain.

Novel H1N1 influenza A viral infection complicated by alveolar hemorrhage.

We report a complication of the novel H1N1 influenza A viral infection not yet described during this 2007-2009 pandemic. Pulmonary hemorrhage is a known complication of influenza pneumonia, including well documented reports from previous pandemics. A 57-year-old African American female presented with fevers, progressive shortness of breath, and cough. After being admitted with an initial diagnosis of myocardial infarction, hemoptysis developed. Nasopharyngeal swabs rapid testing was negative for influenza A and B antigen, but a polymerase chain reaction test for influenza A type H1N1 was positive. A fiberoptic bronchoscopy for ongoing hemoptysis demonstrated diffuse erythema and bleeding, and bronchoalveolar lavage was consistent with alveolar hemorrhage. Progressive hypoxemic respiratory failure ensued, eventually leading to her demise. Our case highlights one of the more feared complications that may have been more common in prior outbreaks, such as the 1918 "Spanish Flu." Autopsy studies from the 1918 influenza pandemic found severe tracheobronchitis (oftentimes hemorrhagic), septal edema, necrotizing bronchiolitis, alveolitis, and extensive hemorrhage, as opposed to the more benign laryngitis and tracheobronchitis that is commonplace in other influenza infections. Similar pathology appearances, including pulmonary hemorrhage, have also been described in H5N1 outbreaks in China and Thailand. It is crucial for pandemic preparedness planning that additional careful and complete autopsy study of this present pandemic influenza infection be performed and reported to answer questions regarding the natural history, pathology, and pathogenesis of this novel H1N1 influenza.