Neurological Emergencies in the Intensive Care Unit

Neurological emergencies present a unique challenge in the intensive care unit, requiring rapid evaluation and treatment. There is a complex interplay in critically ill patients, wherein illness affects the brain and the brain can, in turn, affect the illness, making diagnosis and management challenging. In this review, we discuss the diagnosis and management of common neurological issues that may be encountered in the intensive care unit, including elevated intracranial pressure, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, status epilepticus, neurological complications of critical illness, neuromuscular respiratory failure, and neurological complications in the immunocompromised. …

Management of Pulmonary Vasculitis: A Concise Review

The pulmonary vasculitides are an uncommon group of disorders that are characterized by inflammation and necrosis of the blood vessel wall, usually involving the small and medium-sized blood vessels in the lung. Management has traditionally involved the use of immunosuppressive agents and newer adjunctive therapies such as plasmapheresis. Recent trials over the last decade have highlighted the successful use of these agents in treating this life-threatening illness; however, much remains unknown in terms of exact dosing of these agents and duration of treatment. Adverse events from these therapies remain a serious concern requiring close monitoring and a multidisciplinary approach. Other advances in this field include exploration of newer drugs, some of which are currently being used in randomized trials. This review is an update on the advances made in the management of pulmonary vasculitis over recent years, along with a suggested uniform approach to management based on disease severity classification. …

Cough and Nasal Pain: Putting Together an Uncommon Diagnosis

The pulmonary vasculitides include a wide spectrum of disorders that have in common inflammation and destruction of pulmonary blood vessels. Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is the most common of the antineutrophil cytoplasmic antibody–associated small-vessel vasculitides, and affects a number of organ systems. GPA affects a wide age range, although it typically presents in middle adulthood. The classic triad of GPA—upper airway involvement (sinusitis, otitis media, mucosal ulcerations, airway inflammation), lower respiratory tract disease, and glomerulonephritis—is not always evident at presentation. Furthermore, limited forms of GPA occur, in which the expected upper airway and renal involvement may be lacking. The imaging manifestations of GPA commonly include multiple, bilateral nodules or masses, frequently with cavitation or necrosis. Diffuse lung opacity due to alveolar hemorrhage, or tracheobronchial inflammation that may result in stenosis, may be encountered. Systemic GPA may be diagnosed when cytoplasmic antineutrophil cytoplasmic antibody/anti-proteinase 3 antibodies are detected in the proper clinical context, but, often, the diagnosis of GPA relies on recognition of a combination of common clinical, laboratory, and imaging findings with typical histopathologic changes noted from a biopsy of the affected tissue. A combination of a corticosteroid and immunomodulatory agents is used to induce and maintain remission in patients with GPA. Although potentially fatal if untreated, immunosuppressive therapy has dramatically improved survivorship in patients with GPA. …

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: The Doctors are In, but the Jury is Still Out

Despite attempts to optimize outcomes in acute respiratory distress syndrome (ARDS) using mechanical ventilation and medical management, the mortality associated with this syndrome remains very high. The use of extracorporeal membrane oxygenation (ECMO), particularly veno-venous ECMO (VV-ECMO), as a rescue therapy has grown significantly in recent decades. This review outlines the risks and benefits of ECMO for the treatment of ARDS, examines the body of evidence behind this practice, including 4 randomized controlled trials and 2 case-controlled studies, and discusses the remaining questions and directions for future research. Because VV-ECMO is far more frequently used in the treatment of ARDS than veno-arterial ECMO, referral to ECMO in this review will imply VV-ECMO unless specifically stated. …

Bronchoscopy in the Immunosuppressed Patient

Bronchoscopy in the immunosuppressed patient is routinely undertaken, as mortality of immunosuppressed hosts with pulmonary infiltrates is high. Generally, complications from bronchoscopy are rare, with pneumothorax and respiratory failure being the most serious. Immunosuppressed hosts do not have a higher complication rate than the general patient. In patients with HIV, bronchoscopy should be undertaken even if sputum samples are negative when suspicion is high for Pneumocystis jirovecii or tuberculosis. Patients with a hematologic malignancy have a high incidence of pulmonary infiltrates, and delaying bronchoscopy can significantly reduce the diagnostic yield of a causative agent. Diagnostic testing should include galactomannan levels if the concern is high, even if serum testing is negative. Transbronchial biopsy does not increase the yield of an organism. In patients with stem cell and solid organ transplant, fungal and viral studies including galactomannan should be sent, and diffuse alveolar hemorrhage should be ruled out. Diagnostic bronchoscopy for pulmonary infiltrates in the immunosuppressed host is both a relatively safe and useful tool for increasing identification of an offending pathogen in the setting of a pulmonary infiltrate. Given the high morbidity and mortality associated with many of these disease processes, quick identification and pathology-directed treatment is necessary. Myth: Bronchoscopy in immunosuppressed patients for evaluation of pulmonary infiltrates is a high risk but high yield procedure. …

Rituximab in Connective Tissue Disease–associated Interstitial Lung Disease: A Community-based Experience and Review of Literature

Interstitial lung disease (ILD) is an important manifestation of the connective tissue disorders (CTD), which can lead to significant morbidity and mortality. Conventional therapy involves immunosuppression. Rituximab (RTX), a chimeric monoclonal antibody leading to B-cell depletion, appears to have some benefit in different forms of CTD-ILD. Our community-based, university-affiliated ILD clinic receives referrals from various medical practitioners in the community, including non-university based rheumatologists. The approach to the assessment and management of these patients is multidisciplinary and involves discussions with our center’s radiologists, pathologists (as applicable) and the referring rheumatologists (either university-affiliated or community-based). Therapy is initiated or changed in collaboration with the involved rheumatologists. Patients are followed clinically, functionally (using pulmonary function tests and 6-minute-walk testing), and radiologically using high-resolution chest computed tomography scans (HRCT). Among the patients referred to our clinic with CTD-ILD, six of them received RTX primarily for progressive pulmonary disease. The mean age was 51 years. All the patients were women. One patient had mixed connective tissue disease (MCTD), one patient had Sjögren’s syndrome, one patient had polymyositis, one patient had rheumatoid arthritis and two patients had antisynthetase syndrome. Among the six patients, community-based rheumatologists in private practice were managing four. Two patients received RTX prior to referral to our clinic. Four of the six patients demonstrated clinical improvement and stability in their lung function while on RTX. Three of the six patients demonstrated definite radiologic improvements. One patient developed anaphylactic symptoms and one patient developed a life-threatening infection. There is a growing body of medical…

Pulmonary Vasculitides: A Review

Vasculitides are uncommon diseases that target multiple sites of the respiratory tract. Their manifestations vary widely, ranging from the banal (cough, rash) to life threatening (renal failure, diffuse alveolar hemorrhage). Small-vessel, antineutrophil cytoplasmic antibody–associated vasculitides are the principal forms affecting the lungs. Less often, larger vessel and immune-complex vasculitides afflict the respiratory tract, although the management of these conditions often mirrors that of the antineutrophil cytoplasmic antibody–associated vasculitides with immunosuppression and supplemental modalities such as plasma exchange. This paper reviews the epidemiology and clinical presentation of vasculitides with pulmonary involvement. The review also includes a pragmatic, evidence-based approach to management driven by disease severity. …

CAL02 Liposomes and Other Antitoxins: A New Generation of Anti-Infectives

While new generations of existing classes of antibiotics have predominated pipelines, novel nonantibiotic approaches such as antitoxins are gradually taking a more prominent position to address today’s most challenging issues in the field, notably the threatening rise of resistant strains and the unacceptably high rates of treatment failure and mortality despite the best of care. This review presents the clinical stage broad-spectrum antitoxin agent CAL02, which is active against both gram-positive and gram-negative bacteria including ESKAPE pathogens. CAL02 neutralizes bacterial pore-forming toxins, enzymes, and toxin-effector virulent appendages that play a vital and upstream role in pathogenic processes responsible for the progress and severity of infections such as severe pneumonia, bacteremia, and sepsis. The present overview underlines how combination therapies with antimicrobial agents operating in synergy with antibiotics, via unprecedented mechanisms of action, hold promise to dramatically improve standard of care and overturn the morbidity and mortality associated with resistant pathogens. The concerted efforts of academia, industry, clinicians, and regulatory agencies are contributing to a more accurate understanding of the various nontraditional approaches in development. Novel antitoxin treatments help reshape the antibiotic-driven set of mind. …

Tranexamic Acid for Hemoptysis: A Review

Tranexamic acid (TXA) is an antifibrinolytic agent used to promote hemostasis. TXA is widely used to arrest bleeding in trauma, perioperatively after cardiac surgery, for menorrhagia, and in hemophilia. Less attention has been given to using TXA to lessen hemoptysis, which is the subject of this systematic review. Three small, underpowered randomized controlled trials have examined the efficacy of TXA in hemoptysis. Two of these assessed intravenous TXA, one of which showed significant reduction in the severity and duration of hemoptysis. The third trial examined oral TXA for controlling hemoptysis and failed to show a significant reduction in the amount or duration of hemoptysis. Although inhaled TXA has been described in several case reports and small series, no trial has examined the efficacy of inhaled TXA. The weight of evidence suggests that systemic administration of TXA is safe and does not increase the risk for thrombosis; no adverse effects have been described in the few available reports of inhaled TXA. Overall, TXA is an underrecognized treatment that may have temporizing value in managing patients with nonmassive hemoptysis. In the context that the available literature is sparse, large, well-designed clinical trials are needed to advance understanding of the role of TXA in hemoptysis. …