Management Strategies for Acute Pulmonary Embolism in the ICU.

TOPIC IMPORTANCE: Acute pulmonary embolism (PE) is a common disease encountered by pulmonologists, cardiologists, and critical care physicians throughout the world. For patients with high-risk acute PE (defined by systemic hypotension) and intermediate high-risk acute PE (defined by the absence of systemic hypotension, but the presence of numerous other concerning clinical and imaging features), intensive care often is necessary. Initial management strategies should focus on optimization of right ventricle (RV) function while decisions about advanced interventions are being considered. REVIEW FINDINGS: We reviewed the existing literature of various vasoactive agents, IV fluids and diuretics, and pulmonary vasodilators in both animal models and human trials of acute PE. We also reviewed the potential complications of endotracheal intubation and positive pressure ventilation in acute PE. Finally, we reviewed the data of venoarterial extracorporeal membrane oxygenation (ECMO) use in acute PE. The above interventions are discussed in the context of the underlying pathophysiologic features of acute RV failure in acute PE with corresponding illustrations. SUMMARY: Norepinephrine is a reasonable first choice for hemodynamic support with vasopressin as an adjunct. IV loop diuretics may be useful if evidence of RV dysfunction or volume overload is present. Fluids should be given only if concern exists for hypovolemia and absence of RV dilatation. Supplemental oxygen administration should be considered even without hypoxemia. Positive pressure ventilation should be avoided if possible. venoarterial ECMO cannulation should be implemented early if ongoing deterioration occurs despite these interventions.

Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease.

BACKGROUND: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease. METHODS: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest. RESULTS: From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest. CONCLUSIONS: CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.

Observational cohort study to validate SEARCH, a novel hierarchical algorithm to define long-term outcomes after pulmonary embolism.

BACKGROUND: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but are not defined and quantified sufficiently to serve as outcomes in clinical trials. The planned project will clinically validate a novel method to determine discrete, clinically meaningful diagnoses after acute PE. The method uses an algorithm entitled SEARCH, for symptom screen, exercise testing, arterial perfusion, resting echocardiography, confirmatory imaging and haemodynamic measurements. SEARCH is a stepwise algorithm that sorts patients by a hierarchical series of dichotomous tests into discreet categories of long-term outcomes after PE: asymptomatic, post-PE deconditioning, symptoms from other causes, chronic thromboembolism with ventilatory inefficiency, chronic thromboembolism with small stroke volume augmentation, chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. METHODS: The project will test the inter-rater reliability of the SEARCH algorithm by determining whether it will yield concordant post-PE diagnoses when six independent reviewers review the same diagnostic data on 150 patients evaluated at two time points after PE. The project will also determine whether the post-PE diagnoses are stable, according to the SEARCH algorithm, between the first evaluation and the subsequent one 6 months later. IMPLICATIONS: Validation of the SEARCH algorithm would offer clinicians a straightforward method to diagnose post-PE conditions that are rarely distinguished clinically. Their categorisation and definition will allow post-PE conditions to be used as endpoints in clinical trials of acute PE treatment. TRIAL REGISTRATION NUMBER: NCT05568927.

Cardiopulmonary exercise testing during follow-up after acute pulmonary embolism.

BACKGROUND: Cardiopulmonary exercise testing (CPET) may provide prognostically valuable information during follow-up after pulmonary embolism (PE). Our objective was to investigate the association of patterns and degree of exercise limitation, as assessed by CPET, with clinical, echocardiographic and laboratory abnormalities and quality of life (QoL) after PE. METHODS: In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3- and 12-month follow-ups, including CPET. We defined cardiopulmonary limitation as ventilatory inefficiency or insufficient cardiocirculatory reserve. Deconditioning was defined as peak O2 uptake (V'O2 ) <80% with no other abnormality. RESULTS: Overall, 396 patients were included. At 3 months, prevalence of cardiopulmonary limitation and deconditioning was 50.1% (34.7% mild/moderate; 15.4% severe) and 12.1%, respectively; at 12 months, it was 44.8% (29.1% mild/moderate; 15.7% severe) and 14.9%, respectively. Cardiopulmonary limitation and its severity were associated with age (OR per decade 2.05, 95% CI 1.65-2.55), history of chronic lung disease (OR 2.72, 95% CI 1.06-6.97), smoking (OR 5.87, 95% CI 2.44-14.15) and intermediate- or high-risk acute PE (OR 4.36, 95% CI 1.92-9.94). Severe cardiopulmonary limitation at 3 months was associated with the prospectively defined, combined clinical-haemodynamic end-point of "post-PE impairment" (OR 6.40, 95% CI 2.35-18.45) and with poor disease-specific and generic health-related QoL. CONCLUSIONS: Abnormal exercise capacity of cardiopulmonary origin is frequent after PE, being associated with clinical and haemodynamic impairment as well as long-term QoL reduction. CPET can be considered for selected patients with persisting symptoms after acute PE to identify candidates for closer follow-up and possible therapeutic interventions.

Evaluation of Dyspnea and Exercise Intolerance After Acute Pulmonary Embolism.

Long-term dyspnea and exercise intolerance are common clinical problems after acute pulmonary embolism. Unfortunately, no single test can distinguish among the range of potential pathologic outcomes after pulmonary embolism. We illustrate a stepwise approach to post-pulmonary embolism evaluation that uses a hierarchic series of clinically validated diagnostic tests. The algorithm is represented by the acronym SEARCH, which stands for Symptom screening, Exercise testing, Arterial perfusion, Resting echocardiography, Confirmatory chest imaging, and Hemodynamics measured by right heart catheterization. We illustrate the algorithm with a patient whom we saw in our pulmonary embolism follow-up clinic. Patients are asked at least 6 months after pulmonary embolism whether they have returned to their baseline level of respiratory comfort and exercise tolerance. Patients with dyspnea and exercise intolerance undergo noninvasive cardiopulmonary exercise testing to identify elevated ventilatory dead space ratios, decreased stroke volume augmentation with exercise, and other physiologic abnormalities during exertion. Ventilation-perfusion scanning is performed on those patients with exercise-related physiologic findings to confirm the presence of residual pulmonary arterial obstruction or to suggest alternative diagnoses. Resting echocardiography may provide evidence of pulmonary hypertension; confirmatory imaging with pulmonary angiography or CT angiography may disclose findings characteristic of chronic pulmonary artery obstruction. Finally, right heart catheterization is performed to confirm chronic thromboembolic pulmonary hypertension; if resting pulmonary hemodynamics are normal, then invasive cardiopulmonary exercise testing may disclose exercise-induced defects.

Vacuum exhausted isolation locker (VEIL) to reduce inpatient droplet/aerosol transmission during COVID-19 pandemic.

The vacuum-exhausted isolation locker (VEIL) provides a safety barrier during the care of COVID-19 patients. The VEIL is a 175-L enclosure with exhaust ports to continuously extract air through viral particle filters connected to hospital suction. Our experiments show that the VEIL contains and exhausts exhaled aerosols and droplets.

Pulmonary Embolism Does Not Have an Unusually High Incidence Among Hospitalized COVID19 Patients.

INTRODUCTION: Acute respiratory illnesses from COVID19 infection are increasing globally. Reports from earlier in the pandemic suggested that patients hospitalized for COVID19 are at particularly high risk for pulmonary embolism (PE). To estimate the incidences of PE during hospitalization for COVID19, we performed a rigorous systematic review of published literature. METHODS: We searched for case series, cohort studies and clinical trials from December 1, 2019 to July 13, 2020 that reported the incidence of PE among consecutive patients who were hospitalized for COVID19 in ICUs and in non-ICU hospital wards. To reflect the general population of hospitalized COVID19 patients, we excluded studies in which subject enrollment was linked to the clinical suspicion for venous thromboembolism (VTE). RESULTS: Fifty-seven studies were included in the analysis. The combined random effects estimate of PE incidence among all hospitalized COVID19 patients was 7.1% (95% CI: 5.2%, 9.1%). Studies with larger sample sizes reported significantly lower PE incidences than smaller studies (r2 = 0.161, p = 0.036). The PE incidence among studies that included 400 or more patients was 3.0% (95% CI: 1.7%, 4.6%). Among COVID19 patients admitted to ICUs, the combined estimated PE incidence was 13.7% (95% CI: 8.0%, 20.6%). The incidence of ICU-related PE also decreased as the study sample sizes increased. The single largest COVID19 ICU study (n = 2215) disclosed a PE incidence of 2.3% (95% CI: 1.7%, 3.0%). CONCLUSION: PE incidences among hospitalized COVID19 patients are much lower than has been previously postulated based on smaller, often biased study reports. The incidence of "microthrombosis," leading to occlusion of microscopic blood vessels, remains unknown.

Diagnosis and Treatment of Pulmonary Embolism During the Coronavirus Disease 2019 Pandemic: A Position Paper From the National PERT Consortium.

The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge. Guidelines have delineated how best to diagnose and manage patients with PE. However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms. Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care. The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis. The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects. This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19.

Dyspnea Postpulmonary Embolism From Physiological Dead Space Proportion and Stroke Volume Defects During Exercise.

BACKGROUND: Many patients with pulmonary embolism (PE) report dyspnea on exertion following long-term treatment. Increased physiological dead space proportion (VD/VT) and decreased cardiac stroke volume reserve may distinguish persistent effects of PE itself from symptoms reflecting comorbid conditions or deconditioning. METHODS: This retrospective study analyzed a consecutive series of incremental symptom-limited cardiopulmonary exercise tests that had been ordered to evaluate persistent dyspnea on exertion following long-term treatment for acute PE. Physiological VD/VT was determined at anaerobic threshold from exhaled CO2 and transcutaneous Pco2 (validated against Paco2 measurements). Cardiac stroke volume reserve was estimated at rest and at anaerobic threshold by using oxygen consumption/pulse and previously validated estimates of the arteriovenous oxygen content difference. RESULTS: Cardiopulmonary exercise tests were performed on 40 patients with post-PE dyspnea. In 65.0% (95% CI, 50.2-79.8), VD/VT at anaerobic threshold was abnormally elevated, stroke volume reserve was decreased, or both defects occurred. VD/VT at anaerobic threshold was abnormally elevated (≥ 0.27) in 35.0% (95% CI, 20.2-49.8). VD/VT at anaerobic threshold significantly correlated with the extent of unmatched perfusion defects on subsequent ventilation-perfusion scans (P = .0085). In 55.0% (95% CI, 39.6-70.4), stroke volume reserve at anaerobic threshold was abnormally decreased (≤ 128% of the resting value). Both defects were present in 25.0% (95% CI, 11.6-38.4). CONCLUSIONS: Increased VD/VT at anaerobic threshold and decreased stroke volume reserve during exercise are common among patients with dyspnea on exertion after long-term treatment of PE. The defects can be disclosed noninvasively by using cardiopulmonary exercise testing.

Orthodontic referral management systems: Do they make a difference?

AIMS: To assess the performance of the referral management system (RMS) compared to a previous paper-based referral system and to determine whether referrals reflected the patients' malocclusion and met current guidelines. DESIGN: Three-cycle audit. SETTING: Orthodontic Department, Liverpool University Dental Hospital, UK. PARTICIPANTS: Consecutive new orthodontic patient referrals. METHODS: Data were collected prospectively from orthodontic referral letters and new patient clinic proformas (2016-2017). Cycle 1 assessed the original paper-based referral form, Cycle 2 assessed the first RMS online form and Cycle 3 assessed a modified RMS form. RESULTS: Cycles 1, 2 and 3 audited 83, 84 and 81 referrals, respectively. Agreement between the reason for referral and the new patient clinic findings was moderate for Cycles 1 and 3 (Kappa = 0.47 and 0.60, respectively) and fair for Cycle 2 (Kappa = 0.40). In Cycles 1, 2 and 3, the proportion of new patients appropriate for hospital orthodontic care reduced from 52% to 51% and 40%, respectively. None of the three cycles reached the 90% target for compliance with current referral guidelines. CONCLUSIONS: Cycle 3's RMS form gave a truer reflection of the patients' malocclusion but reduced the proportion of appropriate referrals. Further audit is required in this area to investigate the cost-effectiveness and clinical benefits of the RMS.

Perfusion Scintigraphy in Diagnosis and Management of Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of acute pulmonary embolism (PE). Because the treatment of CTEPH is markedly different from that of other types of pulmonary hypertension, lung ventilation-perfusion (V/Q) scintigraphy is recommended for the workup of patients with unexplained pulmonary hypertension. Lung V/Q scintigraphy is superior to CT pulmonary angiography for detecting CTEPH. Perfusion defect findings of CTEPH can be different from those of acute PE. Familiarity with the patterns of perfusion defects seen during the initial workup of CTEPH and the expected posttreatment changes seen at follow-up imaging is essential for accurate interpretation of V/Q scintigraphy findings. ©RSNA, 2019.

Fibrinogen and the prediction of residual obstruction manifested after pulmonary embolism treatment.

Residual pulmonary vascular obstruction (RPVO) and chronic thromboembolic pulmonary hypertension (CTEPH) are both long-term complications of acute pulmonary embolism, but it is unknown whether RPVO can be predicted by variants of fibrinogen associated with CTEPH.We used the Akaike information criterion to select the best predictive models for RPVO in two prospectively followed cohorts of acute pulmonary embolism patients, using as candidate variables the extent of the initial obstruction, clinical characteristics and fibrinogen-related data. We measured the selected models' goodness of fit by analysis of deviance and compared models using the Chi-squared test.RPVO occurred in 29 (28.4%) out of 102 subjects in the first cohort and 46 (25.3%) out of 182 subjects in the second. The best-fit predictive model derived in the first cohort (p=0.0002) and validated in the second cohort (p=0.0005) implicated fibrinogen Bß-chain monosialylation in the development of RPVO. When the derivation procedure excluded clinical characteristics, fibrinogen Bß-chain monosialylation remained a predictor of RPVO in the best-fit predictive model (p=0.00003). Excluding fibrinogen characteristics worsened the predictive model (p=0.03).Fibrinogen Bß-chain monosialylation, a common structural attribute of fibrin, helped predict RPVO after acute pulmonary embolism. Fibrin structure may contribute to the risk of developing RPVO.

Flow Decay: A Novel Spirometric Index to Quantify Dynamic Airway Resistance.

BACKGROUND: Dynamic airway resistance from obstructive disease causes a concavity in the mid-expiratory portion of the spirometric flow-volume loop. We developed a simple model to measure the exponential decay in air flow during forced exhalation to quantify the extent of dynamic airway obstruction and facilitate the detection of obstructive airway diseases clinically. METHODS: We calculated flow decay as the slope of volume versus ln(1/flow) in mid-exhalation. We derived the normal range in a derivation group of healthy volunteers in whom spirometry had been performed repeatedly. We validated the derived upper limit of normal (mean + 2 × SD) by using it to distinguish a separate group of healthy subjects (n = 25) from subjects with independently diagnosed reversible airway obstruction (n = 31) and subjects with obstruction, hyperinflation, and air trapping (n = 62). RESULTS: In the derivation group (n = 7), the mean ± SD flow decay was 0.588 ± 0.107 L-1 (upper limit of normal = 0.802 L-1). Flow decay in 23 of 25 healthy subjects in the validation group was below the upper limit of normal. In contrast, it was above the upper limit of normal in 29 of 31 subjects with reversible airway obstruction (sensitivity 94%, 95% CI 79-99%; specificity 92%, 95% CI 74-99%) and in 59 of 62 of subjects with obstruction, hyperinflation, and air trapping (sensitivity 92%, 95% CI 74-99%; specificity 95%, 95% CI 86-99%). CONCLUSIONS: Flow decay distinguished subjects with obstructive lung defects from healthy subjects. It is a straightforward representation of spirometry data that provides a reproducible index to quantify dynamic airway obstruction.

Respiratory Compromise as a New Paradigm for the Care of Vulnerable Hospitalized Patients.

Acute respiratory compromise describes a deterioration in respiratory function with a high likelihood of rapid progression to respiratory failure and death. Identifying patients at risk for respiratory compromise coupled with monitoring of patients who have developed respiratory compromise might allow earlier interventions to prevent or mitigate further decompensation. The National Association for the Medical Direction of Respiratory Care (NAMDRC) organized a workshop meeting with representation from many national societies to address the unmet needs of respiratory compromise from a clinical practice perspective. Respiratory compromise may arise de novo or may complicate preexisting lung disease. The group identified distinct subsets of respiratory compromise that present similar opportunities for early detection and useful intervention to prevent respiratory failure. The subtypes were characterized by the pathophysiological mechanisms they had in common: impaired control of breathing, impaired airway protection, parenchymal lung disease, increased airway resistance, hydrostatic pulmonary edema, and right-ventricular failure. Classification of acutely ill respiratory patients into one or more of these categories may help in selecting the screening and monitoring strategies that are most appropriate for the patient's particular pathophysiology. Standardized screening and monitoring practices for patients with similar mechanisms of deterioration may enhance the ability to predict respiratory failure early and prevent its occurrence.

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report.

BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics. METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence. RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C). CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.

Chronic thromboembolic pulmonary hypertension-associated dysfibrinogenemias exhibit disorganized fibrin structure.

INTRODUCTION: Mechanisms contributing to the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) are poorly understood. This disorder is characterized by incomplete resolution of pulmonary perfusion defects resulting from acute venous thromboembolism. We previously identified several dysfibrinogenemias in some patients with CTEPH. The purpose of this study was to determine whether fibrin clot architecture might be implicated in the thrombolytic resistance in patients with these CTEPH-associated dysfibrinogenemias. MATERIALS AND METHODS: Purified fibrinogen from patients and healthy controls was clotted with thrombin in the presence of calcium. Clot turbidity, porosity, and susceptibility to fibrinolysis were evaluated by spectrophotometric and permeation analyses. Fibrin network structure was assessed by laser-scanning confocal microscopy. RESULTS: Compared to normal fibrinogen, CTEPH-associated dysfibrinogenemias exhibited low clot turbidity, decreased porosity, and fibrinolytic resistance. In addition, the dysfibrinogenemias exhibited a more disorganized fibrin network structure characterized by thinner fibers, greater network dispersal and more extensive fiber branching. CONCLUSIONS: Abnormal clot architecture and fibrinolytic resistance may contribute to incomplete clot resolution following acute venous thromboembolism in patients with CTEPH-associated dyfibrinogenemia.

Why acute pulmonary embolism becomes chronic thromboembolic pulmonary hypertension: clinical and genetic insights.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication that affects a small but appreciable percentage of patients after acute pulmonary embolism. The cause of CTEPH is under investigation, but no single causative mechanism has yet been identified. RECENT FINDINGS: CTEPH is likely a complication of residual thrombotic material in the pulmonary arteries that becomes transformed into intravascular scars. Pulmonary artery residua are relatively common after acute pulmonary embolism, and CTEPH may be an extreme manifestation of this phenomenon. Several intriguing observations have been made in patients with CTEPH that give insights into the mechanisms responsible for its formation. Two general pathways have been investigated: resistance of thromboemboli to lysis and attenuation of cellular processes involved in thrombus resolution. This review discusses the evidence supporting each pathway as a mechanism for CTEPH formation, as well as the interaction between the two. SUMMARY: CTEPH may be due to a complex interaction between thrombotic/thrombolytic processes and angiogenic cellular remodeling of organized thrombi. The factors involved may, in fact, vary among CTEPH patients. An understanding of the interplay between the factors that cause CTEPH may help quantify the risk of its occurrence and provide insights into how it can be prevented.