Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012-2021.

The American College of Chest Physicians (CHEST) Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (ie, GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currenrtly relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications.

Well-being at a Military Medical School and Implications for Military Retention.

INTRODUCTION: Physical and psychological well-being play a critical role in the academic and professional development of medical students and can alter the trajectory of a student's quality of personal and professional life. Military medical students, given their dual role as officer and student, experience unique stressors and issues that may play a role in their future intentions to continue military service, as well as practice medicine. As such, this study explores well-being across the 4 years of medical school at Uniformed Services University (USU) and how well-being relates to a student's likelihood to continue serving in the military and practicing medicine. METHODS: In September 2019, 678 USU medical students were invited to complete a survey consisting of three sections-the Medical Student Well-being Index (MSWBI), a single-item burnout measure, and six questions regarding their likelihood of staying in the military and medical practice. Survey responses were analyzed using descriptive statistics, analysis of variance (ANOVA), and contingency table analysis. Additionally, thematic analysis was conducted on open-ended responses included as part of the likelihood questions. RESULTS: Our MSWBI and burnout scores suggest that the overall state of well-being among medical students at USU is comparable to other studies of the medical student population. ANOVA revealed class differences among the four cohorts, highlighted by improved well-being scores as students transitioned from clerkships to their fourth-year curriculum. Fewer clinical students (MS3s and MS4s), compared to pre-clerkship students, indicated a desire to stay in the military. In contrast, a higher percentage of clinical students seemed to "reconsider" their medical career choice compared to their pre-clerkship student counterparts. "Medicine-oriented" likelihood questions were associated with four unique MSWBI items, whereas "military-oriented" likelihood questions were associated with one unique MSWBI item. CONCLUSION: The present study found that the overall state of well-being in USU medical students is satisfactory, but opportunities for improvement exist. Medical student well-being seemed to have a stronger association with medicine-oriented likelihood items than with military-oriented likelihood items. To obtain and refine best practices for strengthening engagement and commitment, future research should examine if and how military and medical contexts converge and diverge throughout training. This may enhance the medical school and training experience and, ultimately, reinforce, or strengthen, the desire and commitment to practice and serve in military medicine.

Antithrombotic Therapy in Arterial Thrombosis and Thromboembolism in COVID-19: An American College of Chest Physicians Expert Panel Report.

BACKGROUND: Evidence increasingly shows that the risk of thrombotic complications in COVID-19 is associated with a hypercoagulable state. Several organizations have released guidelines for the management of COVID-19-related coagulopathy and prevention of VTE. However, an urgent need exists for practical guidance on the management of arterial thrombosis and thromboembolism in this setting. RESEARCH QUESTION: What is the current available evidence informing the prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19? STUDY DESIGN AND METHODS: A group of approved panelists developed key clinical questions by using the Population, Intervention, Comparator, and Outcome (PICO) format that address urgent clinical questions regarding prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19. Using MEDLINE via PubMed, a literature search was conducted and references were screened for inclusion. Data from included studies were summarized and reviewed by the panel. Consensus for the direction and strength of recommendations was achieved using a modified Delphi survey. RESULTS: The review and analysis of the literature based on 11 PICO questions resulted in 11 recommendations. Overall, a low quality of evidence specific to the population with COVID-19 was found. Consequently, many of the recommendations were based on indirect evidence and prior guidelines in similar populations without COVID-19. INTERPRETATION: The existing evidence and panel consensus do not suggest a major departure from the management of arterial thrombosis according to recommendations predating the COVID-19 pandemic. Data on the optimal strategies for prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19 are sparse. More high-quality evidence is needed to inform management strategies in these patients.

Outcomes Associated With Intensive Care and Organ Support Among Patients With COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Accurate accounting of coronavirus disease 2019 (COVID-19) critical care outcomes has important implications for health care delivery. RESEARCH QUESTION: We aimed to determine critical care and organ support outcomes of intensive care unit (ICU) COVID-19 patients and whether they varied depending on the completeness of study follow-up or admission time period. STUDY DESIGN AND METHODS: We conducted a systematic review and meta-analysis of reports describing ICU, mechanical ventilation (MV), renal replacement therapy (RRT), and extracorporeal membrane oxygenation (ECMO) mortality. A search was conducted using PubMed, Embase, and Cochrane databases.We included English language observational studies of COVID-19 patients, reporting ICU admission, MV, and ICU case fatality, published from December 1, 2019 to December 31, 2020. We excluded reports of less than 5 ICU patients and pediatric populations. Study characteristics, patient demographics, and outcomes were extracted from each article. Subgroup meta-analyses were performed based on the admission end date and the completeness of data. RESULTS: Of 6,778 generated articles, 145 were retained for inclusion (n = 60,357 patients). Case fatality rates across all studies were 34.0% (95% CI = 30.7%, 37.5%, P < 0.001) for ICU deaths, 47.9% (95% CI = 41.6%, 54.2%, P < 0.001) for MV deaths, 58.7% (95% CI = 50.0%, 67.2%, P < 0.001) for RRT deaths, and 43.3% (95% CI = 31.4%, 55.4%, P < 0.001) for extracorporeal membrane oxygenation deaths. There was no statistically significant difference in ICU and organ support outcomes between studies with complete follow-up versus studies without complete follow-up. Case fatality rates for ICU, MV, and RRT deaths were significantly higher in studies with patients admitted before April 31st 2020. INTERPRETATION: Coronavirus disease 2019 critical care outcomes have significantly improved since the start of the pandemic. Intensive care unit outcomes should be evaluated contextually (study quality, data completeness, and time) for the most accurate reporting and to effectively guide mortality predictions.

Thromboprophylaxis in Patients With COVID-19: A Brief Update to the CHEST Guideline and Expert Panel Report.

BACKGROUND: Patients hospitalized with COVID-19 often exhibit markers of a hypercoagulable state and have an increased incidence of VTE. In response, CHEST issued rapid clinical guidance regarding prevention of VTE. Over the past 18 months the quality of the evidence has improved. We thus sought to incorporate this evidence and update our recommendations as necessary. STUDY DESIGN AND METHODS: This update focuses on the optimal approach to thromboprophylaxis in hospitalized patients. The original questions were used to guide the search, using MEDLINE via PubMed. Eight randomized controlled trials and one observational study were included. Meta-analysis, using a random effects model, was performed. The panel created summaries using the GRADE Evidence-to-Decision framework. Updated guidance statements were drafted, and a modified Delphi approach was used to obtain consensus. RESULTS: We provide separate guidance statements for VTE prevention for hospitalized patients with acute (moderate) illness and critically ill patients in the ICU. However, we divided each original question and resulting recommendation into two questions: standard prophylaxis vs therapeutic (or escalated dose) prophylaxis and standard prophylaxis vs intermediate dose prophylaxis. This led to a change in one recommendation, and an upgrading of three additional recommendations based upon higher quality evidence. CONCLUSIONS: Advances in care for patients with COVID-19 have improved overall outcomes. Despite this, rates of VTE in these patients remain elevated. Critically ill patients should receive standard thromboprophylaxis for VTE, and moderately ill patients with a low bleeding risk might benefit from therapeutic heparin. We see no role for intermediate dose thromboprophylaxis in either setting.

Executive Summary: Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.

Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.

BACKGROUND: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. METHODS: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. RESULTS: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. CONCLUSION: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.

Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.

BACKGROUND: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. METHODS: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. RESULTS: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. CONCLUSION: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.

Should patients be able to follow commands prior to extubation?

The determination of optimal timing of liberation from mechanical ventilation requires a thorough assessment of multiple variables that can result in extubation failure. It is estimated that 5-20% of extubations fail. Traditional weaning parameters fail to predict extubation failure accurately, and attention has thus turned to improvements in extubation decision making through assessment of elements that may result in inability to protect the airway, such as excessive respiratory secretions, inadequate cough, and depressed mental status. Extubation is particularly controversial in patients with depressed mental status and inability to follow commands. When looking at univariate analyses, the reported studies are relatively evenly divided among those that did and did not find that inability to follow commands (ie, abnormal mental status) increases the risk of extubation failure. In addition, although extubation failure is a risk factor for poor overall outcome in heterogeneous populations, its impact on the patient failing with neurologic dysfunction has not been adequately determined. One limiting factor in all reported studies is how "inability to follow commands" is defined. The majority of studies use the Glasgow coma score, but this is difficult to determine in the intubated patient. Moreover, using the cutoff of Glasgow coma score >or= 8, favored by many authors, is questionable, as some patients with higher scores may be unable to follow commands. Currently it is agreed that many patients who are unable to follow commands, but have the ability to clear pulmonary secretions, can be safely extubated. A prospective, randomized trial using a more specific definition of "following commands" would certainly help remove some of the uncertainty in this patient population.

Should tracheostomy be performed as early as 72 hours in patients requiring prolonged mechanical ventilation?

Advances in treating the critically ill have resulted in more patients requiring prolonged airway intubation and respiratory support. If intubation is projected to be longer than several weeks, tracheostomy is often recommended. Tracheostomy offers the potential benefits of improved patient comfort, the ability to communicate, opportunity for oral feeding, and easier, safer nursing care. In addition, less need for sedation and lower airway resistance (than through an endotracheal tube) may facilitate the weaning process and shorten intensive care unit and hospital stay. By preventing microaspiration of secretions, tracheostomy might reduce ventilator-associated pneumonia. There is controversy, however, over the optimal timing of the procedure. While there have been many randomized controlled trials on tracheostomy timing, most were insufficiently powered to detect important differences, and systematic reviews and meta-analyses are limited by the heterogeneity of the primary studies. Based on the available data, we think it is reasonable to perform early tracheostomy in all patients projected to require prolonged mechanical ventilation. Unfortunately, identifying those patients can be difficult, and for many patient populations we lack the necessary tools to predict prolonged ventilation. We propose an early-tracheostomy decision algorithm.

Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report.

BACKGROUND: Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE. This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. METHODS: A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. RESULTS: The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. CONCLUSIONS: The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

Novel quantitative echocardiographic parameters in acute PE.

BACKGROUND: The tricuspid annular plane systolic excursion (TAPSE) and the right ventricular performance index (RVPI) are quantitative measurements that are valid predictors of clinical outcomes in CHF, MI, PAH, and chronic pulmonary disease. We sought to measure TAPSE and RVPI in patients diagnosed with acute pulmonary embolism (APE) to assess for correlation with known predictors of clinical outcomes. METHODS: Patients admitted with APE had echocardiograms performed within 24 h of diagnosis and B-type natriuretic peptide (BNP) drawn on admission. Serial troponins were measured for the first 48 h of the hospital stay, and clinical course was followed until discharge. RESULTS: A total of 29 patients were enrolled in the study. Compared to those with a normal study, significantly more patients with an abnormal TAPSE had an elevated BNP (60% vs. 5%; P = 0.004) and troponin (50% vs. 11.1%; P = 0.042). The mean TAPSE was 22.3 mm when BNP was normal and 17.4 mm when elevated (P = 0.003). TAPSE values were significantly lower in patients with abnormal RV function by echocardiogram graded by a blinded cardiologist (17.6 mm vs. 21.7 mm; P = 0.03). Both TAPSE and RVPI correlated significantly with septal flattening, RVEDD, and RVEDD/LVEDD by echo. CONCLUSIONS: TAPSE has good correlation with surrogate markers for morbidity and mortality in APE, and both TAPSE and RVPI seem to perform as well as the standard echo parameters used to assess RV function. Both are objective and easy to measure, and therefore warrant prospective study in larger patient groups, with assessment of clinical outcomes.

ACR Appropriateness Criteria® Radiologic Management of Venous Thromboembolism-Inferior Vena Cava Filters.

Venous thromboembolism (VTE)-deep vein thrombosis and pulmonary embolism-is a common cause of morbidity and mortality. The mainstay of VTE prophylaxis and therapy is anticoagulation. In select patients with VTE, inferior vena cava (IVC) filters are used to prevent pulmonary embolism by trapping emboli as they pass from the lower extremity venous system through the IVC. These guidelines review the indications for placement of IVC filters in acute and chronic VTE, as well as the indications for retrieval of implanted IVC filters. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis.

BACKGROUND: Venous thromboembolism (VTE) remains a major cause of morbidity following stroke. The optimal form of pharmacologic prophylaxis following stroke is unknown. METHODS: We identified randomized trials comparing unfractionated heparin (UFH) to low-molecular-weight heparin (LMWH) for VTE prevention in ischemic stroke patients. We focused on the risk for VTE, pulmonary embolism (PE), bleeding, and mortality as a function of the type of agent used for prophylaxis. Findings were pooled with a random-effects model. RESULTS: We identified three trials including 2,028 patients. Two of the studies were blinded, two studies relied on enoxaparin, while one study utilized certoparin. In two studies, UFH was administered three times a day, while it was administered twice daily in the remaining study. The use of LMWH was associated with a significant risk reduction for any VTE (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41 to 0.70; p < 0.001). Limiting the analysis to proximal VTEs also indicated that LMWHs were superior (OR with LMWH vs UFH, 0.53; 95% CI, 0.37 to 0.75; p < 0.001). LMWH use led to fewer PEs as well (OR, 0.26; 95% CI, 0.07 to 0.95; p = 0.042). There were no differences in rates of overall bleeding, intracranial hemorrhage, or mortality based on the type of agent employed. Restricting the analysis to the reports employing enoxaparin did not alter our findings. CONCLUSIONS: The prophylactic use of LMWH compared to UFH following ischemic stroke is associated with a reduction in both VTE and PE. This benefit is not associated with an increased incidence of bleeding. Broader use of LMWH for VTE prevention after ischemic stroke is warranted.

Prevention of venous thromboembolism in neurosurgery: a metaanalysis.

BACKGROUND: Venous thromboembolism (VTE) is an important complication of neurosurgery. Current guidelines recommend pharmacologic prophylaxis in this setting with either unfractionated heparin or low-molecular-weight heparin (LMWH). We conducted a systematic review asking, "Among patients undergoing neurosurgical procedures, how safe and effective is the prophylactic use of heparin and mechanical devices?" METHODS: We searched the medical literature to identify prospective trials reporting on VTE prevention (either mechanical or pharmacologic). The rates of VTE and bleeding were our primary end points and were pooled using a random-effects model. RESULTS: We identified 30 studies reporting on 7,779 patients. There were 18 randomized controlled trials and 12 cohort studies. The results of pooled relative risks (RRs) showed LMWH and intermittent compression devices (ICDs) to be effective in reducing the rate of deep vein thrombosis (LMWH: RR, 0.60; 95% confidence interval [CI], 0.44 to 0.81; ICD: RR, 0.41; 95% CI, 0.21 to 0.78). Similar results were seen when pooled rates from all 30 trials were analyzed. In head-to-head trials, there was no statistical difference in the rate of intracranial hemorrhage (ICH) between therapy with LMWH and nonpharmacologic methods (RR, 1.97; 95% CI, 0.64 to 6.09). The pooled rates of ICH and minor bleeding were generally higher with heparin therapy than with non-heparin-based prophylactic modalities. CONCLUSIONS: In a mixed neurosurgical population, LMWH and ICDs are both effective in the prevention of VTE. Sensitivity analyses have suggested that isolated high-risk groups, such as those with patients undergoing craniotomy for neoplasm, may benefit from a combination of prophylactic methods, suggesting the need for a more individualized approach to these patients.

Controversies in mechanical ventilation: when should a tracheotomy be placed?

With the large and increasing population of mechanically ventilated patients, critical care physicians frequently face the dilemma of whether to perform tracheotomy. The decision is a complex one, requiring a detailed understanding of the risks and benefits of both tracheotomy and prolonged translaryngeal intubation (TLI). It also must be individualized, taking into consideration the patient's preferences and expected clinical course. This article reviews the medical literature regarding the benefits and risks of tracheotomy as compared with TLI. The authors then discuss current data regarding the optimal timing for the procedure and propose an algorithm that may aid intensivists in clinical decision making.

Clinical asthma syndromes and important asthma mimics.

Asthma is a heterogeneous disorder with multiple clinical phenotypes. Phenotypes can be grouped into clinical or physiological, trigger-defined, and inflammatory phenotypes. Treatment based on inflammatory phenotyping improves clinical measures of asthma morbidity. Further study of individual asthma phenotypes will improve understanding of their immunologic and pathologic characteristics and improve diagnosis and therapy. Because asthma is a common disorder with nonspecific presenting features, other disorders are often misdiagnosed as asthma. A high index of suspicion for alternative diagnoses must be maintained when evaluating a patient who presents with clinical features suggestive of asthma, particularly if the patient presents with atypical symptoms or fails to respond to therapy.