Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19.

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

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.

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.

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.

Correction to: Don't Drive Blind: Driving Pressure to Optimize Ventilator Management in ECMO.

The original version of this article unfortunately contained a mistake. The spelling of the Hitoshi Hirose name was incorrect. It was corrected in this erratum.

Don't Drive Blind: Driving Pressure to Optimize Ventilator Management in ECMO.

INTRODUCTION: Driving pressure (DP) while on ECMO has been studied in acute respiratory distress syndrome (ARDS) but no studies exist in those on ECMO without ARDS. We aimed to study association of mortality with DP in all patients on ECMO and compare change in DP before and after initiation of ECMO. METHODS: Consecutive patients placed on ECMO either veno-arterial ECMO or veno-venous ECMO between August 2010 and February 2017 were reviewed. The outcomes were compared based on DP before and after ECMO initiation. RESULTS: A total of 192 patients were included: 68 (35%) had ARDS while 124 (65%) did not. There were 70 individuals for whom DP was available, 33 (47%) had a decrease in DP, whereas 32 (46%) had an increase in DP and 5 (7%) had no change in DP after ECMO initiation. Those with an increase in DP had a higher initial PEEP (14 vs 9 cm H2O, p < 0.001) and a higher PEEP decrease after ECMO (6.4 cm H2O vs by 2.5 cm H2O, p < 0.001). Those with an increase in DP had a significantly longer stay on ECMO than those without (p = 0.022). On multivariable analysis, higher DP 24 h after ECMO initiation was associated with an increase in 30-day mortality (OR 1.15, 75% CI 1.07-1.24, p ≤ 0.001). CONCLUSION: A significant proportion of patients experienced an increase in driving pressure and decrease in compliance after initiation of ECMO. Higher driving pressure after initiation of ECMO is associated with increased adjusted 30-day mortality. Individualized ventilator strategies are needed to reduce mechanical stress while on ECMO.

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.

Observational study of the effect of ketamine infusions on sedation depth, inflammation, and clinical outcomes in mechanically ventilated patients with SARS-CoV-2.

Severely ill patients with COVID-19 are challenging to sedate and often require high-dose sedation and analgesic regimens. Ketamine can be an effective adjunct to facilitate sedation of critically ill patients but its effects on sedation level and inflammation in COVID-19 patients have not been studied. This retrospective, observational cohort study evaluated the effect of ketamine infusions on inflammatory biomarkers and clinical outcomes in mechanically ventilated patients with SARS-CoV-2 infection. A total of 186 patients were identified (47 received ketamine, 139 did not). Patients who received ketamine were significantly younger than those who did not (mean (standard deviation) 59.2 (14.2) years versus 66.3 (14.4) years; P = 0.004), but there was no statistically significant difference in body mass index (P = 0.25) or sex distribution (P = 0.91) between groups. Mechanically ventilated patients who received ketamine infusions had a statistically significant reduction in Richmond Agitation-Sedation Scale score (-3.0 versus -2.0, P < 0.001). Regarding inflammatory biomarkers, ketamine was associated with a reduction in ferritin (P = 0.02) and lactate (P = 0.01), but no such association was observed for C-reactive protein (P = 0.27), lactate dehydrogenase (P = 0.64) or interleukin-6 (P = 0.87). No significant association was observed between ketamine administration and mortality (odds ratio 0.971; 95% confidence interval 0.501 to 1.882; P = 0.93). Ketamine infusion was associated with improved sedation depth in mechanically ventilated COVID-19 patients and provided a modest anti-inflammatory benefit but did not confer benefit with respect to mortality or intensive care unit length of stay.

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.

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.

Systemic Inflammatory Response Syndrome After Extracorporeal Membrane Oxygenation Decannulation in COVID-19 Patients.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is frequently observed following decannulation from extracorporeal membrane oxygenation (ECMO). Differentiating cytokine release due to infection from endothelial injury from cannula removal and/or discontinuation from the ECMO circuit has been shown to impact treatment and outcomes. This response, however, may be complicated in COVID-19 patients due to prevalent glucocorticoid and immune modulator use. It remains unclear whether COVID-19 infection and/or associated immune modulator use impact the incidence of SIRS following decannulation. OBJECTIVES: The aim of this study is to investigate the incidence of the SIRS phenomenon and associated outcomes in patients with COVID-19 after ECMO decannulation. METHODS: An IRB-approved retrospective chart review of all patients who survived ECMO between June 31, 2010 and July 7, 2021 was done to identify patients who experienced SIRS within 48 hours of decannulation from ECMO support. Patients with COVID-19 were confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV2. SIRS was confirmed when two out of three of the following criteria were met: fever, leukocytosis, and/or initiation/escalation of vasopressors. Patients who developed post-ECMO SIRS were then distinguished based on the presence of infection. Infection was defined by the presence of either a new or positive culture following decannulation. We compared the incidence of SIRS and infection within 48 hours of decannulation in patients with and without COVID-19. RESULTS: We identified 227 eligible patients who survived ECMO. Twenty-eight patients (12%) had COVID-19. Of these patients, ten patients with COVID-19 (36%) experienced post-ECMO SIRS, including those with true SIRS (n=3) and associated infections (n=7). Five of the ten patients with COVID-19 who experienced post-ECMO SIRS were exposed to immune modulators within two weeks of decannulation. Ninety-five (42%) patients without COVID-19 developed post-ECMO SIRS. Thirty-day survival in COVID patients who experienced post-ECMO SIRS compared to COVID patients who did not experience post-ECMO SIRS was 73% vs. 94%. (p=0.11). CONCLUSION: Post-ECMO SIRS is common. The incidence of SIRS following decannulation was similar when historically compared to non-COVID patients who survived ECMO in a previously reported cohort from our institution. Immune-modulation exposure within two weeks of decannulation did not affect the incidence of SIRS in patients with COVID-19.

Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

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.

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.

Characteristics of Post-ICU and Post-COVID Recovery Clinics in 29 U.S. Health Systems.

The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

Implementing a collaborative protocol in a sepsis intervention program: lessons learned.

The objective of this prospective cohort study was to see the effect of the implementation of a Sepsis Intervention Program on the standard processes of patient care using a collaborative approach between the Emergency Department (ED) and Medical Intensive Care Unit (MICU). This was performed in a large urban tertiary-care hospital, with no previous experience utilizing a specific intervention program as routine care for septic shock and which has services and resources commonly available in most hospitals. The study included 106 patients who presented to the ED with severe sepsis or septic shock. Eighty-seven of those patients met the inclusion criteria for complete data analysis. The ED and MICU staff underwent a 3-month training period followed by implementation of a protocol for sepsis intervention program over 6 months. In the first 6 months of the program's implementation, 106 patients were admitted to the ED with severe sepsis and septic shock. During this time, the ED attempted to initiate the sepsis intervention protocol in 76% of the 87 septic patients who met the inclusion criteria. This was assessed by documentation of a central venous catheter insertion for continuous SvO(2) monitoring in a patient with sepsis or septic shock. However, only 48% of the eligible patients completed the early goal-directed therapy (EGDT) protocol. Our data showed that the in-hospital mortality rate was 30.5% for the 87 septic shock patients with a mean APACHE II score of 29. This was very similar to a landmark study of EGDT (30.5% mortality with mean APACHE II of 21.5). Data collected on processes of care showed improvements in time to fluid administration, central venous access insertion, antibiotic administration, vasopressor administration, and time to MICU transfer from ED arrival in our patients enrolled in the protocol versus those who were not. Further review of our performance data showed that processes of care improved steadily the longer the protocol was in effect, although this was not statistically significant. There was no improvement in secondary outcomes, including total length of hospital stay, MICU days, and mortality. Implementation of a sepsis intervention program as a standard of care in a typical hospital protocol leads to improvements in processes of care. However, despite a collaborative approach, the sepsis intervention program was underutilized with only 48% of the patients completing the sepsis intervention protocol.

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.

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.

Tocilizumab in the Management of COVID-19: A Preliminary Report.

IMPORTANCE: Pneumonia due to COVID-19 can lead to respiratory failure and death due to the development of the acute respiratory distress syndrome. Tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, is being administered off-label to some patients with COVID-19, and although early small studies suggested a benefit, there are no conclusive data proving its usefulness. OBJECTIVE: To evaluate outcomes in hospitalized patients with COVID-19 with or without treatment with Tocilizumab. DESIGN, SETTING, PARTICIPANTS: Retrospective study of 1938 patients with confirmed COVID-19 pneumonia admitted to hospitals within the Jefferson Health system in Philadelphia, Pennsylvania, between March 25, 2020 and June 17, 2020, of which 307 received Tocilizumab. EXPOSURES: Confirmed COVID-19 pneumonia. MAIN OUTCOMES AND MEASURES: Outcomes data related to length of stay, admission to intensive care unit (ICU), requirement of mechanical ventilation, and mortality were collected and analyzed. RESULTS: The average age was 65.2, with 47% women; 36.4% were African-American. The average length of stay was 22 days with 26.3% of patients requiring admission to the ICU and 14.9% requiring mechanical ventilation. The overall mortality was 15.3%. Older age, admission to an ICU, and requirement for mechanical ventilation were associated with higher mortality. Treatment with Tocilizumab was also associated with higher mortality, which was mainly observed in subjects not requiring care in an ICU with estimated odds ratio (OR) of 2.9 (p = 0.0004). Tocilizumab treatment was also associated with higher likelihood of admission to an ICU (OR = 4.8, p < 0.0001), progression to requiring mechanical ventilation (OR = 6.6, p < 0.0001), and increased length of stay (OR = 16.2, p < 0.0001). CONCLUSION AND RELEVANCE: Our retrospective analysis revealed an association between Tocilizumab administration and increased mortality, ICU admission, mechanical ventilation, and length of stay in subjects with COVID-19. Prospective trials are needed to evaluate the true effect of Tocilizumab in this condition.