Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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'.)
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
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 and VAP 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'.)
Etiology of community-acquired pneumonia (April 2016)
Multiple studies of patients with community-acquired pneumonia (CAP) have identified an etiologic agent in fewer than half of cases. In a study of hospitalized adults with CAP in the United Kingdom that used both bacterial cultures and comprehensive multiplex molecular testing for bacteria and viruses of lower respiratory tract specimens, a pathogen was identified in 87 percent of cases by molecular methods . Culture-based methods detected a pathogen in only 39 percent of cases. Haemophilus influenzae and Streptococcus pneumoniae were the most common agents detected, followed by a wide variety of pathogens. Viruses were present in 30 percent of cases; 82 percent of these were detected in specimens that also tested positive for bacteria. A caveat is that contamination of specimens with upper respiratory tract secretions could cause false positive results . (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Inpatients'.)
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'.)
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
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 "Corticosteroid 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'.)
Simplified approach to acetylcysteine infusion for acetaminophen poisoning (April 2016)
The treatment of acetaminophen poisoning with acetylcysteine is sometimes complicated by nonallergic anaphylactic reactions (NAARs). The results of a large retrospective study, in addition to recent clinical experience, suggest that these reactions can be reduced by using a two-bag regimen instead of the traditional three-bag regimen described in the manufacturer’s package insert and most dosing references. In the study, NAARs occurred in 10 percent of the 389 patients treated with the standard regimen versus 4.3 percent of the 210 patients treated with a modified two-bag regimen . In both regimens, acetylcysteine was infused over 20 hours. While further study is needed to ensure the safety and effectiveness of this regimen, we believe this is a reasonable approach to treatment in adults and older adolescents with acetaminophen poisoning. (See "Acetaminophen (paracetamol) poisoning in adults: Treatment", section on 'Simplified 20 hour IV protocol'.)
QUALITY AND SAFETY
Risk factors associated with readmission (May 2016)
While many hospitalizations are unavoidable, some readmissions are likely preventable, although the proportion that are preventable is uncertain. An observational study including 1000 general medicine patients readmitted within 30 days of discharge to 12 United States academic medical centers found that approximately 27 percent were considered potentially avoidable . Factors most strongly associated with potentially preventable readmissions included decision-making in the emergency department regarding the readmission, failure to relay important information to outpatient providers, premature discharge of patients, and lack of patient and family discussions about goals of care for patients with serious illnesses. (See "Hospital discharge and readmission", section on 'Avoidable versus unavoidable readmissions'.)
- Schaller SJ, Anstey M, Blobner M, et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet 2016; 388:1377.
- Morris PE, Berry MJ, Files DC, et al. Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2016; 315:2694.
- Ray JG, Vermeulen MJ, Bharatha A, et al. Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes. JAMA 2016; 316:952.
- Carson SS, Cox CE, Wallenstein S, et al. Effect of Palliative Care-Led Meetings for Families of Patients With Chronic Critical Illness: A Randomized Clinical Trial. JAMA 2016; 316:51.
- Creamer D, Walsh SA, Dziewulski P, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol 2016; 174:1194.
- Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med 2016; 375:1131.
- Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14:1308.
- Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63:e61.
- Gadsby NJ, Russell CD, McHugh MP, et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis 2016; 62:817.
- Jain S, Pavia AT. Editorial Commentary: The Modern Quest for the "Holy Grail" of Pneumonia Etiology. Clin Infect Dis 2016; 62:826.
- Gaudry S, Hajage D, Schortgen F, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med 2016; 375:122.
- Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA 2016; 315:2190.
- Rothwell PM, Algra A, Chen Z, et al. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet 2016; 388:365.
- Keh D, Trips E, Marx G, et al. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA 2016.
- 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.
- Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol (Phila) 2016; 54:115.
- Auerbach AD, Kripalani S, Vasilevskis EE, et al. Preventability and Causes of Readmissions in a National Cohort of General Medicine Patients. JAMA Intern Med 2016; 176:484.