Showing papers in "Seminars in Respiratory and Critical Care Medicine in 2017"

Management of Acute Respiratory Failure in Pregnancy

Abstract: Respiratory failure affects up to 1 in 500 pregnancies, more commonly in the postpartum period. The causes of respiratory failure include several pregnancy-specific conditions such as preeclampsia, amniotic fluid embolism, and peripartum cardiomyopathy. Pregnancy may also increase the risk or severity of other conditions, such as asthma, thromboembolism, viral pneumonitis, and gastric acid aspiration. Changes to maternal respiratory physiology and the presence of a fetus may affect the assessment and management of these patients. In addition to identifying pregnancy-specific causes, some differences exist in the management of the pregnant woman with acute respiratory failure. Endotracheal intubation in pregnancy carries a significant risk, due to upper airway edema and rapid oxygen desaturation following apnea. Few studies have addressed prolonged mechanical ventilation management in pregnancy. Optimizing oxygenation is important, but whether permissive hypercapnia is tolerated during pregnancy remains unclear. Delivery of the fetus is often considered but does not always improve maternal respiratory function and should be reserved only for cases where benefit to the fetus is anticipated.

Infections Due to Acinetobacter baumannii in the ICU: Treatment Options.

Abstract: Bacteria within the genus Acinetobacter (principally A baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that may cause nosocomial infections in critically ill or debilitated patients (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds) Treatment of Acinetobacter infections is difficult, as Acinetobacter spp are intrinsically resistant to multiple antimicrobial agents, and have a remarkable ability to acquire new resistance determinants via mechanisms that include plasmids, transposons, integrons, and resistance islands Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC Global spread of multidrug-resistant (MDR)-A baumannii strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive use of antibiotics amplifies this spread Many isolates are resistant to all antimicrobials except colistin (polymyxin E) and tigecycline, and some infections are untreatable with existing antimicrobial agents Antimicrobial resistance poses a serious threat to treat or prevent infections due to ABC Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes

Massive Pulmonary Embolism: Extracorporeal Membrane Oxygenation and Surgical Pulmonary Embolectomy.

Abstract: Massive pulmonary embolism (PE) refers to large emboli that cause hemodynamic instability, right ventricular failure, and circulatory collapse. According to the 2016 ACCP Antithrombotic Guidelines, therapy for massive PE should include systemic thrombolytic therapy in conjunction with anticoagulation and supportive care. However, in patients with a contraindication to systemic thrombolytics or in those who fail the above interventions, extracorporeal membrane oxygenation (ECMO) and/or surgical embolectomy may be used to improve oxygenation, achieve hemodynamic stability, and successfully treat massive PE. Randomized controlled human trials evaluating ECMO in this context have not been done, and its role has not been well-defined. The European Society of Cardiology 2014 acute PE guidelines briefly mention that ECMO can be used for massive PE as a method for hemodynamic support and as an adjunct to surgical embolectomy. The 2016 CHEST Antithrombotic Therapy for venous thromboembolism Disease guidelines do not mention ECMO in the management of massive PE. However, multiple case reports and small series cited benefit with ECMO for massive PE. Further, ECMO may facilitate stabilization for surgical embolectomy. Unfortunately, ECMO requires full anticoagulation to maintain the functionality of the system; hence, significant bleeding complicates its use in 35% of patients. Contraindications to ECMO include high bleeding risk, recent surgery or hemorrhagic stroke, poor baseline functional status, advanced age, neurologic dysfunction, morbid obesity, unrecoverable condition, renal failure, and prolonged cardiopulmonary resuscitation without adequate perfusion of end organs. In this review, we discuss management of massive PE, with an emphasis on the potential role for ECMO and/or surgical embolectomy.

Emergence of Antimicrobial Resistance among Pseudomonas aeruginosa: Implications for Therapy.

Abstract: Pseudomonas aeruginosa (PA), a nonlactose fermenting gram-negative bacillus, is a common cause of nosocomial infections in critically ill or debilitated patients, particularly ventilator-associated pneumonia (VAP), and infections of bloodstream, urinary tract, intra-abdominal, wounds/skin/soft tissue PA rarely affects healthy individuals, but may cause serious infections in patients with chronic structural lung disease, comorbidities, advanced age, impaired immune defenses, or with medical devices (eg, urinary or intravascular catheters, foreign bodies) Treatment of pseudomonal infections is difficult, as PA is intrinsically resistant to multiple antimicrobials, and may acquire new resistance determinants even while on antimicrobial therapy Mortality associated with pseudomonal VAP or bacteremias is high (> 35%) and optimal therapy is controversial Over the past three decades, antimicrobial resistance among PA has escalated globally, via dissemination of several international multidrug-resistant “epidemic” clones We review the emergence of antimicrobial resistance to this pathogen, and discuss approaches to therapy (both empirical and definitive)

Ocular Involvement in Sarcoidosis

Abstract: Ocular involvement in sarcoidosis occurs in ∼40% and the eye is the presenting organ in roughly 20%. The course of ocular disease does not necessarily parallel that of systemic disease. Uveitis is the most common presentation and shows mainly a chronic course; anterior uveitis is associated with better visual prognosis than posterior localization. Painful bilateral anterior granulomatous uveitis most commonly occurs in black patients at younger age, while painless posterior bilateral involvement with peripheral multifocal choroiditis is commonly seen in elderly white females. Patients with posterior uveitis develop often ocular complications and central nervous system involvement. Vitritis, segmental periphlebitis, choroidal granulomas, and peripheral multifocal chorioretinitis are often seen clinical features. Optic nerve involvement is uncommon, but if present, results often in poor visual outcome. Lacrimal gland and conjunctival involvement are also common and present clinically as dry eyes or remain asymptomatic with good visual prognosis. Sarcoidosis-associated uveitis is mostly managed by local treatment with steroid drops or periocular and intraocular steroid injections or with novel intraocular corticosteroid implants. Patients with sight-threatening disease or optic nerve involvement need systemic therapy. Systemic therapy is based on a step-up regimen where corticosteroids are used in the initial phase of the disease and if long-term treatment is required, steroid-sparing immunomodulatory drugs are implemented such as methotrexate or biological agents. Despite the mainly chronic course, need for long-term treatment, and frequent ocular surgeries in the majority of patients, the visual outcome of sarcoidosis-associated uveitis is fairly good if therapy has started on time.

Oropharyngeal Decontamination with Antiseptics to Prevent Ventilator-Associated Pneumonia: Rethinking the Benefits of Chlorhexidine

Abstract: Daily oral care with chlorhexidine for mechanically ventilated patients is ubiquitous in contemporary intensive care practice. The practice is predicated upon meta-analyses suggesting that adding chlorhexidine to daily oral care regimens can reduce ventilator-associated pneumonia (VAP) rates by up to 40%. Close analysis, however, raises three concerns: (1) the meta-analyses are dominated by studies in cardiac surgery patients in whom average duration of mechanical ventilation is

Asthma during Pregnancy: Exacerbations, Management, and Health Outcomes for Mother and Infant.

Abstract: One in 10 pregnant women worldwide has asthma and of these, 10% will have a severe exacerbation requiring oral corticosteroids (OCSs) in pregnancy This review of recent publications in the field will describe the effects of exacerbation on maternal and neonatal health, the use of asthma medications during pregnancy, and will suggest novel management approaches for asthma in pregnancy Pregnancy results in unpredictable changes in the disease; therefore, regular monitoring of symptoms is recommended Uncontrolled asthma is frequently described in cohorts of pregnant women with asthma, and some recent studies show associations with adverse perinatal outcomes, as previously demonstrated with exacerbations Guidelines for the management of asthma recommend the continued use of inhaled corticosteroids (ICSs) in pregnancy, with budesonide having a particularly good safety profile Recent data suggest small effects of asthma and/or asthma medication use on congenital malformations; however, there is less data available on the safety of ICS/long-acting β agonist combinations, which are increasingly used for maintenance treatment Novel management strategies are needed to address the complex needs of pregnant women with asthma These include medication nonadherence and the presence of numerous comorbidities which can affect asthma, such as rhinitis, cigarette smoking, obesity, and mental health issues Inflammation-based management has been shown to be effective in reducing exacerbations in pregnancy and may also improve perinatal outcomes The involvement of a multidisciplinary team and the assessment of comorbidities have potential to improve the health of mothers and their offspring

Sarcoidosis-Associated Pulmonary Hypertension.

Abstract: There is growing appreciation for the prevalence and impact of pulmonary hypertension in patients with sarcoidosis (SAPH). This chapter will focus on the pathophysiology of this complication and its association with patients’ outcomes, including functional ability and survival. When to suspect complicating SAPH will be addressed with a suggested work-up algorithm presented. The potential role and data supporting the use of pulmonary vasoactive agents in SAPH will be addressed. However, there is a paucity of data in this area and the need for further investigation in the form of multicenter, double-blind, randomized controlled studies will be underscored.

Aneurysmal Subarachnoid Hemorrhage: Strategies for Preventing Vasospasm in the Intensive Care Unit.

Abstract: This article addresses the intensive care unit (ICU) management of patients with aneurysmal subarachnoid hemorrhage (SAH), with an emphasis on the prevention of cerebral vasospasm and delayed cerebral ischemia (DCI), which are major contributors to morbidity and mortality. Interventions addressing various steps in the development of vasospasm have been attempted, with variable success. Enteral nimodipine remains the only approved measure to potentially prevent DCI. Since oral and intravenous administrations are limited by hypotension, direct administration via sustained-release pellets and intraventricular administration of sustained-release microparticles are being investigated. Studies of other calcium channel blockers have been disappointing. Efforts to remove blood from the subarachnoid space via cisternal irrigation, cisternal or ventricular thrombolysis, and lumbar cerebrospinal fluid drainage have met with limited and variable success, and they remain an area of active investigation. Several interventions that had early promise have failed to show benefit when studied in large trials; these include tirilazad, magnesium, statins, clazosentan, transluminal angioplasty, and hypervolemia.

Löfgren's Syndrome: Diagnosis, Management, and Disease Pathogenesis.

Abstract: Lofgren's syndrome (LS), first described in 1946 by Swedish Professor of Medicine Sven Lofgren, is a clinically distinct phenotype of sarcoidosis. Patients typically experience an acute disease onset, usually with fever, and characteristic symptoms of bilateral hilar lymphadenopathy, erythema nodosum, and/or bilateral ankle arthritis or periarticular inflammation. LS patients are well documented to have a good prognosis, which is especially true for HLA-DRB1*03+ individuals. The presence of this allele correlates closely with an accumulation of clonal CD4+ T-cell populations in the lung, suggestive of local antigen recognition. Moreover, LS differs markedly from “non-LS” sarcoidosis regarding immune cell activation, differentiation, and regulation, which may influence clinical outcome and spontaneous disease resolution. This review offers an overview of the clinical characteristics, genetic background, and immunological characteristics of LS, as well as patient management, and reflections on future scientific challenges, emphasizing the concept of LS as a disease in its own right.

Ventilator-Associated Pneumonia: The Role of Emerging Diagnostic Technologies.

Abstract: Antibiotic resistance has emerged as a key determinant of outcome in patients with serious infections along with the virulence of the underlying pathogen. Within the intensive care unit (ICU) setting, ventilator-associated pneumonia (VAP) is a common nosocomial infection that is frequently caused by multidrug-resistant bacteria. Antimicrobial resistance is a growing challenge in the care of critically ill patients. Escalating rates of antibiotic resistance add substantially to the morbidity, mortality, and cost related to infection in the ICU. Both gram-positive organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-intermediate S. aureus, and gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter species, carbapenem-resistant Enterobacteriaceae, such as the Klebsiella pneumoniae carbapenemase–producing bacteria, and extended spectrum β-lactamase organisms, have contributed to the escalating rates of resistance seen in VAP and other nosocomial infections. The rising rates of antimicrobial resistance have led to the routine empiric administration of broad-spectrum antibiotics even when bacterial infection is not documented. Moreover, there are several new broader-spectrum antibiotics that have recently become available and others scheduled for approval in the near future. The challenge to ICU clinicians is how to most effectively utilize these agents to maximize patient benefits while minimizing further emergence of resistance. Use of rapid diagnostics may hold the key for achieving this important balance. There is an urgent need for integrating the administration of new and existing antibiotics with the emerging rapid diagnostic technologies in a way that is both cost-effective and sustainable for the long run.

Quality of Life in Sarcoidosis.

Abstract: Health-related quality of life (HRQL) is an important aspect of patient evaluation. HRQL is particularly important in sarcoidosis, where treatment decisions are often based on HRQL impairment. HRQL assessment in sarcoidosis must take into account not only the direct effects of the disease but also the disease's psychosocial and emotional impact as well as the potential toxicity of therapy. Patient-reported outcomes (PROs) have been used to assess HRQL in sarcoidosis cohorts. Recent HRQL PROs have been developed that are sarcoidosis-specific and have adequate resolution to be used for monitoring individual patients potentially. In this article, the approach to HRQL assessment in sarcoidosis is discussed. This article focuses on the general approach to HRQL assessment, specific sarcoidosis issues concerning HRQL assessment, the construction of HRQL PROs, and their application in sarcoidosis. Several HRQL issues in sarcoidosis will be specifically highlighted, including parasarcoidosis syndromes, sarcoidosis-induced fatigue, and the impact of corticosteroid therapy.

Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Abstract: Sarcoidosis is a disorder of unknown etiology. It is a systemic disease, frequently involving the lungs, skin, eyes, and lymph nodes. It is characterized by formation of noncaseating granulomas at the site(s) of disease. Sarcoidosis has a complex disease pathogenesis, with involvement of both the innate and adaptive immune systems. Several innate immune system receptors including NOD-like receptors and Toll-like receptors appear to be involved in the development of sarcoidosis as well as cellular players such as dendritic cells and macrophages. Furthermore, lymphocytes from the adaptive immune system including Th1, Th17, regulatory T cells, and B cells are likely to play a role in the sarcoidosis disease pathogenesis as well. Possibly, genetic susceptibility and exposure to particular etiologic agents including mycobacterial and propionibacterial antigens, metals, and silica can cause sarcoidosis. Besides exogenous triggers, also self-compounds such as serum amyloid A and vimentin, have been found to play a role in the development of sarcoidosis. It is likely that sarcoidosis does not have one single cause but rather is the result of the interplay between different etiologic agents and the immune system in predisposed individuals.

Imaging in Neurocritical Care Practice.

Abstract: The use of neuroimaging in conjunction with serial neurological examinations is a core component of modern neurocritical care practice. Although there is a growing role for other neuromonitoring techniques, the ability to quickly and accurately interpret images in the context of a patient's clinical status arguably remains the indispensable skill for neurocritical care practitioners. Due to its rapid acquisition time and excellent ability to detect intracerebral hemorrhage (ICH), cerebral edema, and signs of elevated intracranial pressure, computed tomography (CT) remains the most useful neuroimaging technique for intensive care unit (ICU) patients. An emergent head CT is obtained to inform most time-sensitive decisions that arise in the neurological ICU (NICU). CT features also figure prominently in prognostic scores for common NICU conditions such as traumatic brain injury (TBI), ICH, and subarachnoid hemorrhage (SAH). Among patients who are sufficiently stable to leave the ICU and lie flat for an extended period, magnetic resonance imaging provides much more detailed, high-contrast images which can aid in the detection of ischemia, diffuse axonal injury, and neuroprognostication. Though primarily used in neurocritical care research, nuclear medicine imaging techniques have some clinical applications, particularly in ancillary testing for brain death. Finally, as in the field of critical care as a whole, formal and point-of-care ultrasound studies are increasingly utilized in the NICU, and are an important tool in the neurointensivist's armamentarium. We review here the common applications of imaging in the neurocritical care setting. As ICU patients are frequently unstable and their risk of clinical decompensation increases substantially during transport away from the ICU, guidelines and recommendations for maximizing patient safety during transport to radiology studies are also explored.

Imaging for Sarcoidosis.

Abstract: Sarcoidosis is a systemic disease characterized by widespread development of noncaseating epithelioid granulomas. Based on a joint statement by the American Thoracic Society (ATS), European Thoracic Society (ERS), and the World Association for Sarcoidosis and other Granulomatous Disorders (WASOG), the diagnosis of sarcoidosis requires a compatible clinical picture, histologic demonstration of noncaseating granulomas, and exclusion of other diseases that may give a similar histologic or clinical picture. Although to a casual reader these recommendations suggest that making a diagnosis of sarcoidosis is straightforward, a consensus on the diagnostic role of imaging in sarcoidosis remains unclear. First, despite the primacy of chest computed tomography (CT) for evaluating diffuse lung disease, a guideline-based diagnosis of sarcoidosis without biopsy requires specific appearances on chest radiography (Lofgren's syndrome) or 67Ga Scintigraphy (Heerfordt's syndrome). Second, although the literature on CT as a prognostic tool in interstitial lung disease is relatively extensive, very little of this focuses specifically on sarcoidosis. Third, staging of sarcoidosis relies on radiographic appearances at presentation using a system devised by Scadding more than 40 years ago. This is in stark contrast to idiopathic pulmonary fibrosis where significant advances have been made in imaging-based staging and computer-assisted quantification of disease in the past 10 years. In this article, in addition to describing the myriad of imaging patterns seen in sarcoidosis, the impact imaging has on diagnosis, staging, and prediction of outcome will also be discussed. Cardiac-related sarcoidosis and neurosarcoidosis will be discussed in separate articles.

Pulmonary Infections in Pregnancy.

Abstract: Pregnant women experience physiological and immunological changes that increase the risk or severity of certain pulmonary infections. These changes also affect drug disposition, which impacts treatment choices. In this article, we review the available data on (1) the physiological and immunological changes that specifically impact tuberculosis, influenza, and varicella pneumonia; (2) active and latent tuberculosis management, including drug monitoring and maternal–infant outcomes; (3) the treatment and prevention of influenza; and (4) the diagnosis and management of varicella pneumonia. Clinical trials often exclude pregnant women, but there is a consensus that treating pregnant women for tuberculosis, influenza, and varicella pneumonia improves outcomes for both the woman and her child.

Systemic Thrombolytic Therapy for Acute Pulmonary Embolism: Who Is a Candidate?

Abstract: Pulmonary embolism (PE) is a major cause of both acute and long-term morbidity for a large number of patients worldwide, and massive PE is frequently fatal. Right ventricular (RV) dysfunction is a key determinant of prognosis in the acute phase of PE. Patients with clinically overt RV failure, that is, with cardiogenic shock or persistent hypotension at presentation (acute high-risk PE), are clearly in need of immediate reperfusion treatment with systemic thrombolysis or, alternatively, surgical or catheter-directed techniques. On the other hand, within the large group of patients presenting without hemodynamic instability, the bleeding risk of full-dose intravenous thrombolytic treatment has been shown to outweigh its benefits, even if they present with evidence of both RV dysfunction and myocardial injury. Thus, current guidelines agree in proposing a strategy of effective anticoagulation and "watchful waiting" (with initial hemodynamic monitoring notably over the first 48-72 hours) in intermediate-risk PE, with an indication for rescue thrombolysis if signs of hemodynamic decompensation appear. Recently published trials suggest that catheter-directed, ultrasound-assisted, low-dose local fibrinolysis may provide an effective and particularly safe treatment option for some of these patients. Ongoing or planned studies are expected to resolve the controversy on the efficacy and safety or reduced-dose systemic thrombolysis and to address the possible impact of thrombolytic therapy on long-term outcomes after acute PE.

Bringing Emergency Neurology to Ambulances: Mobile Stroke Unit.

Abstract: Ischemic stroke results from blocked arteries in the brain, with earlier thrombolysis with intravenous tissue plasminogen activator (tPA) and/or mechanical thrombectomy resulting in improved clinical outcomes. Mobile Stroke Unit (MSU) can speed up the treatment with tPA and facilitate faster triage for patients to hospitals for mechanical thrombectomy. The first registry-based MSU study in Germany demonstrated faster treatment times with tPA using a MSU, a higher proportion of patients being treated within the first "golden hour," and a suggestion of improved 3-month clinical outcomes. The first multicenter, prospective, randomized clinical trial comparing MSU versus standard care was started in 2014 after the launch of the MSU in Houston, TX, demonstrating the feasibility and safety of MSU operation in the United States, and reliability of telemedicine to evaluate stroke patients for tPA eligibility. Although conclusive evidence from clinical trials to support MSUs as being cost effective and improving clinical outcomes is still needed, there are a myriad of other clinical and research applications of MSUs that could have profound implications for managing patients with neurological emergencies.

Ictal-Interictal Continuum: When to Worry About the Continuous Electroencephalography Pattern.

Abstract: Continuous electroencephalography (cEEG) monitoring is an invaluable tool in the evaluation of encephalopathy and coma in critically ill patients. Marked increases in cEEG monitoring, coinciding with several societal guideline statements in the last decade, have allowed earlier detection and treatment of clearly harmful patterns, including nonconvulsive seizures (NCSz) and nonconvulsive status epilepticus (NCSE). However, it has also unmasked a range of EEG patterns of less clear clinical significance, with some more “malignant” than others given their potential association with increased neuronal stress and secondary brain injury. These patterns lay on a spectrum often referred to as the ictal-interictal continuum (IIC). To date, no definitive guidelines exist for the management of these potentially harmful EEG patterns, thus presenting a clinical dilemma for critical care physicians. Here, we review the various IIC patterns, their associated features, seizure risk, and outcomes and also propose a clinical approach to management based on the available data and expert opinion.

How Should We Treat Hospital-Acquired and Ventilator-Associated Pneumonia Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae?

Abstract: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) due to extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) represent a growing problem Indeed, ESBL-PE is endemic in many countries, and 5 to 25% of intensive care unit (ICU) patients are ESBL-PE carrier on ICU admission ESBL-PE HAP/VAP is associated with a higher mortality than HAP/VAP due to susceptible Enterobacteriaceae because the resistance profile decreases the adequacy rate of empiric therapy ESBL-PE should be considered in the empirical treatment in case of the high burden of ESBL-PE in the unit, in the case of previous ESBL-PE colonization, when the HAP/VAP occurs late, and in patients with shock A negative active systematic surveillance culture on rectal swab reduced the risk of ESBL-PE VAP to less than 1% Rapid diagnostic tests are now able to confirm the presence of ESBL-PE in VAP within 24 hours; new molecular methods will provide results within few hoursAdequate treatment usually required carbapenems The alternative β-lactams such as β-lactams/β-lactamases inhibitor combinations could be proposed as a step-down therapy according to the antibiotic susceptibility result Optimization of pharmacokinetics requires high dosage and continuous or prolonged infusions for β-lactams When the patient is stabilized, a therapy of duration 7 to 8 days is recommended

Blood Pressure Management for Acute Ischemic and Hemorrhagic Stroke: The Evidence.

Abstract: Hypertension is the most common modifiable risk factor for stroke (both ischemic and hemorrhagic types). In the hyperacute phase, a majority of patients shows an elevated blood pressure (BP) at the time of presentation because of sympathetic hyperactivity or a physiological response to tissue ischemia. Therefore, BP may decrease spontaneously in a few hours and may drop further when complete recanalization is achieved. In stroke guidelines, an elevated BP is usually left untreated up to a systolic BP (SBP) of 220 mm Hg and a diastolic BP of 120 mm Hg. This recommendation is based on the BP level that corresponds to the upper limit of the pressure autoregulation zone above which cerebral blood flow is directly dependent on BP. However, in patients in whom administration of recombinant tissue-type plasminogen activator is indicated, BP should be controlled to a level

Management of Cerebral Edema in Acute Liver Failure.

Abstract: Advances in medical care of the acute liver failure patient have led to a significant reduction in mortality related to the condition. Nevertheless, cerebral edema and ensuing brain herniation remains one of the top causes of demise in acute liver failure. Controversy remains regarding the utility of invasive intracranial pressure monitoring as well as usage of novel treatment modalities including therapeutic hypothermia. This review provides a brief summary into the pathophysiology and risk factors for developing cerebral edema in the context of acute liver failure; this review particularly provides a practical focus on general management of the patient with established cerebral edema as well as specific intracranial pressure-lowering strategies.

Who Is Safe to Extubate in the Neuroscience Intensive Care Unit

Abstract: Patients admitted to the neuroscience intensive care unit (NICU) may have respiratory compromise from either central or peripheral neurological pathology, and may hence require intubation and mechanical ventilation for very diverse reasons. Liberation from invasive ventilation, that is, extubation, at the earliest possible time is a widely accepted principle in intensive care. For this, classic extubation criteria have been established in the general critical care setting, mainly targeting pulmonary function and cooperativeness of the patient. However, classic extubation criteria have failed to predict successful extubation in many studies on NICU patients, and extubation failure (EF) rates range between ∼20 and 40% in these. Not necessarily impaired consciousness, but neurological impairment of securing the airway and handling secretions (dysphagia, low pharyngeal muscle tone, weak cough, etc.) may be mainly responsible for this dilemma. Attempts have been made to identify predictors of EF or success, and to establish extubation scores for the NICU, but results have been partially controversial and the database is still weak. It is very important to have a stepwise protocol to approach extubation in the NICU patient and to be prepared for reintubation (at times in a difficult airway) and alternatives (such as tracheostomy). The particular challenges of safely extubating the NICU patient will be the focus of this review, including a suggestion for a standardized approach.

Reversal of Direct Oral Anticoagulants: Current Status and Future Directions.

Abstract: Direct oral anticoagulants (DOACs) are increasingly used for prevention and treatment of venous thromboembolism and for prevention of stroke in patients with nonvalvular atrial fibrillation. In phase III clinical trials that included more than 100,000 patients, the DOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with less serious bleeding, particularly less intracranial bleeding. Real-world evidence supports these outcomes. Despite this, some physicians and patients are concerned about serious bleeding or emergencies unless specific reversal agents for the DOACs are available. However, in clinical trials performed without reversal agents, the outcome of major bleeds was similar or better in patients receiving DOACs than in those taking VKAs. Because of their short half-lives, supportive measures are sufficient to manage most bleeds in patients receiving DOACs. Anticoagulant reversal should only be considered with life-threatening bleeds, with bleeds that fail to respond to usual measures and in patients requiring urgent surgery. Idarucizumab is licensed for dabigatran reversal and andexanet alfa is likely to be soon licensed for reversal of rivaroxaban, apixaban, and edoxaban. To ensure responsible use of these agents, every hospital needs a bleeding management algorithm that identifies patients eligible for reversal and outlines appropriate dosing regimens.

General Care of the Pregnant Patient in the Intensive Care Unit

Abstract: Pregnant women represent a small subset of all intensive care unit (ICU) admissions and may require intensive care for “obstetric” or “nonobstetric” reasons. Women may be admitted to the ICU at any stage of pregnancy or in the postpartum period. Pregnancy may be discovered at the time of admission to the ICU. Pregnancy impacts on ICU care in a variety of ways and requires a multidisciplinary approach to management. Pregnancy is associated with considerable physiological changes that affect most organ systems, including an expansion in blood volume, an increase in minute ventilation, and an increased risk of thrombosis. The enlarging uterus may be associated with mechanical complications due to compression and displacement of other structures. The growing fetus places considerable demands upon the mother, being reliant on maternal systems for oxygenation, nutrition and disposal of carbon dioxide, and other waste products. This “second patient” must be considered when managing the pregnant woman. Optimal management of the mother usually constitutes best treatment for the fetus. Maternal shock and physiological disturbance, medications, and ionizing radiation from diagnostic imaging may have harmful effects on the unborn child. Delivery of the fetus for either maternal or fetal indications may be necessary and should be planned for, even if considered unlikely to be required. Care of the postpartum woman has its own challenges, including managing lactation and facilitating mother/infant contact. In this article, the general care aspects of ICU treatment of the pregnant woman will be discussed, including monitoring, physiological target setting, and general supportive care.

Using Ventilator-Associated Pneumonia Rates as a Health Care Quality Indicator: A Contentious Concept.

Abstract: Pneumonia is a leading cause of hospital-acquired infections, although reported rates of ventilator-associated pneumonia (VAP) have been declining in recent years. A multifaceted infection prevention approach, using a “ventilator bundle,” has been shown to reduce the frequency of VAP, while improving other patient outcomes. Because of difficulties in defining VAP, the Center for Medicare and Medicaid Service introduced a new streamlined ventilator-associated event (VAE) definition in 2013 for the surveillance of complications in mechanically ventilated patients. VAE measures are increasingly being measured by institutions in the United States in place of VAP rates and as a potential measure of the quality of intensive care unit (ICU) care. However, there is increased recognition that the streamlined definitions identify a different subset of patients than those identified by traditional VAP surveillance and that VAP prevention strategies may not impact all the causes of VAE. Also, VAP and VAE rates may not always reflect the quality of care in a given ICU, especially since patient factors, beyond the control of the hospital, may impact the rates of VAP and VAE. In this review, we discuss the issues related to VAP as a quality measure and the areas of uncertainty related to the new VAE definitions.

Spontaneous Intraventricular Hemorrhage: When Should Intraventricular tPA Be Considered?

Abstract: Spontaneous intracerebral hemorrhage (ICH) is the most common cause of intraventricular hemorrhage (IVH) in adults. Complicating approximately 40% of ICH cases, IVH adds to the morbidity and mortality of this often fatal form of stroke. It is also a severity factor that complicates subarachnoid hemorrhage and traumatic brain injury, along with other less common causes of intracranial bleeding. Medical and surgical interventions to date have focused on limiting ICH and IVH expansion, controlling intracranial pressure, and relieving obstructive hydrocephalus. The placement of an external ventricular drain (EVD) can achieve the latter two goals but has not demonstrated improvement in clinical outcomes beyond mortality reduction. More recently, intraventricular fibrinolysis, utilizing the EVD, has gained interest as a safe and potentially effective method to maintain catheter patency and facilitate hematoma removal. A recent phase III clinical trial evaluating the efficacy of intraventricular alteplase versus intraventricular saline showed a mortality benefit, but failed to meet the primary endpoint of significant functional improvement. However, planned subgroup analysis focusing on patients with IVH volume > 20 mL, and those with IVH removal > 85% suggest that significant functional benefits may be attainable with this therapy. The practice of intraventricular fibrinolysis for spontaneous IVH is not the standard of care; however, based on 20 years of experience, it meets thresholds as a safe intervention, and in those patients with a high burden of intraventricular blood, aggressive clearance may lead to improved quality of life in survivors of this morbid syndrome.

Current Medical Therapy for Sarcoidosis.

Abstract: Most cases of sarcoidosis are mild and self-limited, with a spontaneous cure. However, in some patients, this disease may also be life-threatening, particularly when severe manifestations induce vital organ dysfunction. Sarcoidosis may also severely impair the quality of life through diverse, persistent disabling symptoms. To date, there is no curative treatment for sarcoidosis, but only anti-inflammatory drugs limiting the pathologic impact of sarcoidosis in reducing enhanced immunity reactions, granulomatous formation, and their consequences. Current anti-inflammatory treatments for sarcoidosis include corticosteroids as the first-line treatment; disease-modifying antisarcoid drugs, mainly immunosuppressive and immunomodulatory drugs, as second-line treatment; and finally tumor necrosis factor (TNF) inhibitors, as third-line treatment. Corticosteroids are most effective; they give rapid results, sometimes with serious, incremental adverse effects. A second-line treatment, mainly low-dose methotrexate and azathioprine, is indicated in case of corticosteroid resistance, intolerance, or contraindication or more often as a corticosteroid-sparing agent when a prolonged treatment of more than 10 mg/d equivalent prednisone is expected. TNF inhibitors are considered in severe refractory sarcoidosis. Infliximab has been proven effective. Usually, treatment for sarcoidosis lasts up to 1 year or longer. The usual drug regimen is made of an induction and then a maintenance protocol before a step-by-step decrease and eventual withdrawal. Contraindications may exist. Each therapeutic decision must follow a rigorous diagnostic evaluation to determine the disease impact, its outcome (progression or not), and its response to treatment in the long run. Pharmacogenetics is still in its infancy, but could help develop a more personalized therapy. Non anti-inflammatory treatments, such as implantable cardiac devices, are also useful, particularly for some organs. In the end, persistent disabling symptoms are very frequent and call for an accurate diagnosis, which may be difficult to treat.

Pulmonary Hypertension in Pregnancy.

Abstract: Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy associated with abnormal cardiopulmonary hemodynamics and a limited life expectancy due to right heart failure Young women are preferentially affected Women with PAH are at increased risk of complications and death during pregnancy for both the mother and the fetus While it is not well characterized how changes in sex steroids and other hormones during pregnancy affect pulmonary hypertension, many expected systemic and heart–lung physiologic adaptations during gestation are poorly tolerated in women with PAH Despite the approval of numerous therapies for PAH in recent years, pregnancy avoidance or early termination is still recommended in women with PAH because of poor outcomes In this review, we will discuss physiologic and hormonal changes in pregnancy as they relate to pulmonary vascular disease and right heart function We will review current consensus recommendations and outline the management of pregnancy in PAH when it does occur

Pharmacokinetic/Pharmacodynamics-Optimized Antimicrobial Therapy in Patients with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia.

Abstract: Hospital-acquired pneumonia and ventilator-associated pneumonia continue to cause significant morbidity and mortality With increasing rates of antimicrobial resistance, the importance of optimizing antibiotic treatment is key to maximize treatment outcomes This is especially important in critically ill patients in intensive care units, in whom the infection is usually caused by less susceptible organisms In addition, the marked physiological changes that can occur in these patients can cause serious changes in antibiotic pharmacokinetics which in turn alter the attainment of therapeutic drug exposures This article reviews the various aspects of the pharmacokinetic changes that can occur in the critically ill patients, the barriers to achieving therapeutic drug exposures in pneumonia for systemically delivered antibiotics, the optimization for commonly used antibiotics in hospital- and ventilator-associated pneumonia, the agents that should be avoided in the treatment regimen, as well as the use of adjunctive therapy in the form of nebulized antibiotics