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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
GENERAL HOSPITAL MEDICINE
Early mobilization in critically ill patients (July 2016, Modified October 2016)
Two recent trials on the role of physical therapy for early mobilization of critically ill patients report conflicting outcomes:
●One trial of mechanically ventilated surgical intensive care unit (ICU) patients reported that compared with usual care, implementation of a rigid goal-directed early mobilization strategy resulted in improved mobilization scores, decreased ICU length of stay, improved functional mobility at hospital discharge, and possibly improved mortality .
●A single-center trial of 300 critically ill ventilated patients reported no benefit for an intensive daily physical rehabilitation regimen initiated in the ICU and continued until hospital discharge, when compared with usual care (ie, intervention as needed when requested by the health care team) .
Findings from the trial reporting benefit may be more reliable, because the communication loop that was in place ensured that patients actually received the physical therapy intervention. Nonetheless, these findings need to be replicated before early mobilization can be routinely recommended. (See "Post-intensive care syndrome (PICS)", section on 'Prevention'.)
Safety of magnetic resonance imaging and gadolinium in pregnancy (September 2016)
Magnetic resonance imaging (MRI) may be used for diagnostic imaging in pregnancy when ultrasound examination is inadequate; however, fetal safety has not been conclusively established. Recently, the largest study of MRI in pregnancy (over 1700 exposed and 1.4 million unexposed births) reported that first-trimester MRI was not associated with significantly increased risks for stillbirth, neonatal death, congenital anomaly, neoplasm, or vision or hearing loss in children followed up to age four years, when adjustments were made for differences between exposure groups . The study also found that gadolinium exposure at any time during pregnancy was associated with an increased risk for stillbirth and neonatal death. Children exposed in utero were at increased risk for rheumatological, inflammatory, or infiltrative skin conditions, but not congenital anomalies or nephrogenic systemic fibrosis (NSF). This study is a major addition to the body of evidence supporting the safety of MRI in pregnancy when medically indicated. It also provides the first data supporting existing recommendations to avoid use of gadolinium-based contrast agents in pregnant women, when possible. (See "Diagnostic imaging procedures during pregnancy", section on 'Magnetic resonance imaging'.)
Palliative care consultation for families of patients in the intensive care unit (August 2016)
Post-intensive care syndrome-family (PICS-F) is a term given to family members who have been affected physically and psychologically during the intensive care unit (ICU) stay of critically ill patients. Therapeutic measures for PICS-F are poorly studied. One multicenter randomized trial examined the impact of a palliative care-led consultation for surrogate decision-makers of critically ill patients in the ICU who were unlikely to wean from mechanical ventilation . Compared with routine family meetings conducted by the ICU team, palliative care-led consultation did not reduce symptoms of anxiety or depression of family members and may have increased symptoms of posttraumatic stress disorder. However, limitations of this study include possible inadequate "dosing" of the intervention (on average, 1.4 encounters per family and physician presence at only 9 percent of meetings), leaving the possibility that more aggressive and supportive interventions may have different outcomes. (See "Post-intensive care syndrome (PICS)", section on 'Post-intensive care syndrome-family'.)
New guidelines for the management of Stevens-Johnson/toxic epidermal necrolysis syndrome (August 2016)
The British Association of Dermatologists released new guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), a severe and potentially fatal mucocutaneous drug reaction . The guidelines provide evidence-based recommendations for the diagnosis, severity assessment, and management of SJS/TEN. Specific areas covered include initial management, supportive care, and therapies intended to reduce mortality, such as intravenous immune globulins, systemic corticosteroids, and cyclosporine. The treatment of eye involvement, including systemic therapies and amniotic membrane transplantation to prevent permanent ocular sequelae, as well as the management of oral, urogenital, and airway mucosal involvement are also addressed. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'General principles'.)
HOSPITAL CARDIOVASCULAR MEDICINE
Outcomes after PCI in patients with MI after noncardiac surgery (August 2016)
Mortality in patients who sustain a myocardial infarction (MI) after noncardiac surgery is known to be high. Outcomes were evaluated in a cohort of such individuals who were referred for coronary angiography and possible percutaneous coronary intervention (PCI) within seven days of surgery . Among those who ultimately underwent PCI, the 30-day death rate was 31.2 percent in those with ST-elevation MI and 8.5 percent in those with non-ST elevation MI. The optimal management strategy for those patients who sustain an MI in the perioperative period is unknown. (See "Perioperative myocardial infarction after noncardiac surgery", section on 'Prognosis after MI'.)
Transfusion outcomes with "fresh" versus "old" blood (November 2016)
The INFORM trial (Informing Fresh versus Old Red Cell Management) is the largest trial to compare clinical outcomes with "fresh" versus "old" blood . In INFORM, over 20,000 hospitalized adults who required transfusion were randomly assigned to receive "old" red blood cells (RBCs; stored for a mean of 24 days) or "fresh" RBCs (stored for a mean of 13 days). There were no differences in mortality or hospital length of stay. Smaller trials in adults, children, and neonates have also concluded that outcomes are unaffected by RBC storage duration. (See "Red blood cell transfusion in adults: Storage, specialized modifications, and infusion parameters", section on 'Clinical relevance of storage time'.)
Updated guideline and meta-analysis on hemoglobin thresholds for blood transfusion (November 2016)
An updated systematic review and meta-analysis of randomized trials involving over 12,000 patients has provided more support for the use of a restrictive transfusion strategy (giving less blood, transfusing at a lower hemoglobin level, typically 7 to 8 g/dL) for most hemodynamically stable medical and surgical patients who are not actively bleeding or symptomatic from anemia . An updated 2016 guideline from the AABB (an international organization) also supports the use of restrictive thresholds . The major exception is patients with acute coronary syndromes (ACS), for whom data from large randomized trials are not available and for whom pilot trials suggest a more liberal threshold may be associated with better outcomes. We continue to use an individualized approach to transfusion in patients with ACS. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Society guidelines'.)
Investigational reversal agent for factor Xa inhibitors (September 2016)
Andexanet alfa is an investigational reversal agent for anticoagulants that inhibit factor Xa, including the oral direct factor Xa inhibitors, low molecular weight heparins, and fondaparinux. It is a catalytically inactive form of factor Xa that is administered intravenously as a bolus followed by a two-hour infusion. A recent preliminary report from a study in patients with factor Xa inhibitor-associated major bleeding (ANNEXA-4) has now demonstrated efficacy of andexanet, with excellent or good hemostasis in 37 of 47 patients and reduced anti-factor Xa activity for several hours . Potential concerns include a possible increased risk of thrombosis, although most patients in the study were elderly, had atrial fibrillation and/or risk factors for venous thromboembolism, and were not receiving anticoagulation at the time they developed a thrombus. ANNEXA-4 is ongoing; andexanet is not yet available for clinical or compassionate use. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antidotes under development'.)
Dosing of direct oral anticoagulants in obese patients (June 2016)
Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject . The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) ≤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight ≥120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)
HOSPITAL INFECTIOUS DISEASES
M. chimaera infections associated with cardiac surgery (October 2016)
Clusters of disseminated infection with Mycobacterium chimaera in the United States and Europe have been linked to exposure to contaminated Stockert 3T heater-cooler devices during cardiac surgery . In the United States, the Food and Drug Administration recommends retiring 3T heater-cooler devices and accessories that have tested positive for M. chimaera or that have been linked to known infections and refraining from using any 3T heater-cooler device manufactured before September 2014 except in emergency situations. Providers of patients who have undergone cardiac surgery should be aware of the possibility of M. chimaera infection, even months to years following the procedure. (See "Overview of nontuberculous mycobacterial infections in HIV-negative patients", section on 'Disseminated disease'.)
IDSA/ATS guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia (August 2016)
The Infectious Diseases Society of America and the American Thoracic Society have released updated guidelines for the management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) . Empiric therapy for HAP (algorithm 1) and VAP (algorithm 2) should include agents with activity against Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacilli. Choice of a specific regimen for empiric therapy should be based upon knowledge of the prevailing pathogens (and susceptibility patterns) within the healthcare setting as well as risk factors for multidrug resistance in the individual patient. The guidelines emphasize that a seven-day course of antimicrobial therapy is appropriate for most patients rather than a longer duration. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Treatment'.)
Early initiation of renal replacement therapy (June 2016)
It is unclear if the early initiation of renal replacement therapy (RRT) (ie, without an obvious indication such as severe hyperkalemia, metabolic acidosis, pulmonary edema or advanced uremic symptoms) provides any benefit to critically ill patients with acute kidney injury (AKI) compared with later initiations of RRT. Two new randomized trials have evaluated this in somewhat different patient populations. In the larger trial, 620 critically ill patients with severe AKI were randomized to early or delayed RRT . There was no difference in 60-day mortality, and nearly one-half of patients in the delayed RRT group recovered without requiring RRT. In contrast, a second trial of 231 critically ill patients with more moderate AKI showed reduced 90-day mortality with earlier RRT . In the delayed initiation group, only 11 patients ended up not requiring RRT, and early RRT reduced the duration of AKI and length of stay. However, we have lower confidence in the results of the smaller trial, because it is possible that the relatively small size of the trial resulted in an overestimate of the treatment benefit. It is otherwise difficult to understand how minor differences in the protocols and patient populations could achieve such dramatically different outcomes. Until further data are available, UpToDate suggests that RRT not be initiated in the absence of obvious clinical indications. (See "Renal replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Timing of elective initiation'.)
Intravenous carbamazepine approved for use in adults (November 2016)
An intravenous (IV) preparation of carbamazepine has been approved by the US Food and Drug Administration for use as short-term replacement therapy in adult patients on stable doses of oral carbamazepine who are transiently unable to ingest oral preparations . The recommended IV conversion dose is 70 percent of the total daily oral dose, divided into four equal doses and given every six hours. (See "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects", section on 'Carbamazepine'.)
Early benefit of aspirin after TIA or ischemic stroke (July 2016)
The risk of recurrent ischemic stroke is highest in the first days and weeks after a transient ischemic attack (TIA) or ischemic stroke, but the benefit of aspirin in this time period has not been well studied. In a recent pooled analysis of data from over 15,000 subjects in 12 trials evaluating aspirin for secondary prevention, the benefit of aspirin was strongest in the early weeks after TIA or ischemic stroke . Compared with control (mostly placebo), aspirin reduced the relative risk of recurrent ischemic stroke within the first six weeks by 58 percent (1 versus 2.4 percent, absolute risk reduction 1.4 percent). The benefit of aspirin in this time frame was greatest for the subgroup of patients with TIA or minor stroke. These findings emphasize that aspirin should be started as early as possible after the diagnosis of TIA or ischemic stroke is confirmed. (See "Antiplatelet therapy for secondary prevention of stroke", section on 'Aspirin'.)
HOSPITAL PULMONOLOGY AND CRITICAL CARE MEDICINE
Syncope and pulmonary embolus (October 2016)
While pulmonary embolus (PE) has generally been considered to be a relatively rare cause of syncope, a recent study reported a 17 percent prevalence of PE among patients admitted to hospital with syncope, and a 25 percent prevalence among those without an alternative etiology for syncope . Two-thirds of patients with syncope secondary to PE had thrombus located in the mainstem or lobar arteries, suggesting that syncope may indicate a high burden of thrombus. The study underscores the importance of syncope as a presenting manifestation of clinically significant PE. (See "Clinical presentation, evaluation, and diagnosis of the adult with suspected acute pulmonary embolism", section on 'History and examination'.)
High-flow oxygen for the prevention of postextubation respiratory failure (October 2016)
Results from trials that compare high-flow oxygen delivered via nasal cannula (HFNC) and noninvasive ventilation (NIV) for the prevention of postextubation respiratory failure have been conflicting. In a recent multicenter trial of patients at high risk of reintubation following extubation, rates of reintubation, the primary outcome, were similar for NIV and HFNC, and there was no difference in rates of mortality, sepsis, or multiorgan failure . For patients considered at high risk of reintubation, this study supports the use of a trial of HFNC as an alternative to NIV for those at high risk of reintubation. However, given conflicting earlier findings, additional trials are needed to determine strict selection criteria before routinely recommending HFNC for the prevention of postextubation respiratory failure. (See "Extubation management", section on 'High flow oxygen versus noninvasive ventilation'.)
Corticosteroids not beneficial in severe sepsis without shock (October 2016)
The administration of corticosteroids to patients with sepsis is generally reserved for those with septic shock. A recent randomized trial of nearly 400 adults examined the efficacy of corticosteroids in patients with severe sepsis who did not have shock . Compared with placebo, an infusion of hydrocortisone (200 mg daily for five days followed by tapering until day 11) had no effect on mortality or progression to shock. This trial supports our current recommendation that corticosteroids not be routinely administered to septic patients without shock. (See "Glucocorticoid therapy in septic shock", section on 'HYPRESS'.)
Helmet-delivered noninvasive ventilation in acute respiratory distress syndrome (May 2016)
In patients with acute respiratory distress syndrome (ARDS), noninvasive ventilation (NIV) delivered with a face mask is often not sufficient to prevent intubation. Problems include patient discomfort and air leaks. Delivery of NIV using a helmet (ie, a transparent hood that covers the entire head, sealed with a rubber collar at the neck) may circumvent some of these issues. A preliminary trial compared the two approaches by randomly assigning patients with ARDS who required NIV to continue face mask NIV or switch to helmet–delivered NIV . Helmet-delivered NIV reduced the need for intubation (18 versus 62 percent) and increased ventilator-free days. It also reduced length of stay and 90-day mortality without additional adverse effects. While encouraging, early trial termination may have exaggerated the efficacy. In addition, general concerns regarding limited physician experience and unclear guidelines regarding patient selection, optimal ventilator settings, and monitoring need to be addressed before helmet-delivered NIV can be applied as a therapy for patients with ARDS. (See "Mechanical ventilation of adults in acute respiratory distress syndrome", section on 'Invasive versus noninvasive'.)
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- Patel BK, Wolfe KS, Pohlman AS, et al. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 2016; 315:2435.