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What's new in pulmonary and critical care medicine
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2014. | This topic last updated: Apr 10, 2014.

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.


Highly selective COX-2 inhibitors in aspirin-exacerbated respiratory disease (January 2014)

Patients with aspirin-exacerbated respiratory disease (AERD) often have severe hypersensitivity reactions to nonsteroidal antiinflammatory drugs (NSAIDs), which are directly related to inhibition of the enzyme COX-1. Although highly selective COX-2 inhibitors are theoretically safe, observational studies described patients who appeared to react to these agents. In a new meta-analysis of placebo-controlled blinded trials, over 400 patients with AERD were challenged with highly selective (celecoxib, rofecoxib) or relatively selective (ie, meloxicam, nabumetone, nimesulide) COX-2 inhibitors [1]. Whereas 1 in 13 patients had reactions to the relatively selective agents, there were no reactions to the highly selective agents. This analysis supports the safety of highly selective COX-2 inhibitors in patients with AERD. (See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions", section on 'Highly selective COX-2 inhibitors'.)


Combination therapy with umeclidinium and vilanterol for COPD (January 2014)

Patients with COPD who have persistent symptoms despite use of a single long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) inhaler sometimes find relief with the combination of two inhalers. A dry powder inhaler containing both a LAMA and LABA (umeclidinium and vilanterol) has been approved for use in COPD in the United States. The combination was compared with each of the individual agents and placebo in a 24-week randomized trial that included over 1500 subjects with COPD [2]. The combination inhaler achieved greater increases in pulmonary function and improved symptom control compared with the individual agents and placebo. Adverse events were infrequent. The efficacy of the umeclidinium/vilanterol inhaler has not been compared with other currently available LAMAs and LABAs. (See "Management of stable chronic obstructive pulmonary disease", section on 'Combined therapy'.)

Reassuring data about the tiotropium soft mist inhaler (October 2013)

The TIOtropium Safety and Performance In Respimat (TIOSPIR) trial has provided reassuring data about the safety of the tiotropium soft mist inhaler (SMI, Respimat) despite prior analyses that the SMI might carry an increased risk of mortality relative to the tiotropium dry powder inhaler (DPI, Handihaler). In the TIOSPIR trial, over 17,000 patients with COPD were randomly assigned to one of two doses of tiotropium by SMI or to the DPI [3]. After a mean follow-up of 2.3 years, the risk of mortality did not differ between the SMI and DPI groups. While patients with cardiac arrhythmia, ischemic heart disease, and coronary heart disease were included, those with unstable cardiovascular conditions (class III or IV heart failure, myocardial infarction in the prior six months) or moderate or severe renal failure were excluded. Thus, the safety of the tiotropium SMI in these latter groups has not been determined. (See "Role of anticholinergic therapy in COPD", section on 'Mortality'.)


Lower infectious risk with restrictive blood transfusion strategy (April 2014)

A restrictive blood transfusion strategy (eg, transfusion at a hemoglobin level of 7 to 8 g/dL) is associated with a trend towards lower mortality compared with a liberal strategy (transfusion for a hemoglobin level <10 g/dL) in many medical and surgical settings. A new meta-analysis of randomized trials found that a restrictive, compared with a liberal, strategy was associated with a lower risk of serious infections (12 versus 17 percent, respectively) in hospitalized patients [4]. The greatest benefit was seen in patients undergoing orthopedic surgery and those who presented with sepsis. The safety of restrictive transfusion in patients with acute coronary syndromes (eg, myocardial infarction) has not been evaluated adequately, and higher thresholds may be needed in this population. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Overview of our approach'.)

FDA warning about doripenem for ventilator-associated pneumonia (March 2014)

In 2014, the US Food and Drug Administration (FDA) approved revisions to the doripenem label warning clinicians about increased mortality rates in patients who received doripenem rather than imipenem for ventilator-associated bacterial pneumonia, based on results of a randomized trial that was stopped early due to safety concerns [5]. In the intention-to-treat population of the trial, 28-day all-cause mortality was higher and clinical response rates were lower among patients receiving doripenem than in those receiving imipenem, although different dosing regimens and use of adjunctive aminoglycosides may have influenced these results [6]. Doripenem is not approved by the FDA for the treatment of pneumonia. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Gram-negative pathogens'.)

Intensive insulin therapy in critically ill children (January 2014)

In critically ill adults, intensive insulin therapy (IIT) has not been shown to improve survival, and hypoglycemic events due to IIT may be associated with increased mortality. The effects of IIT in critically ill children are less well established. A randomized trial of nearly 1400 children in pediatric surgical intensive care units compared the effects of tight (blood glucose target 72 to 126 mg/dL [4 to 7 mmol/L]) and conventional (target 180 to 216 mg/dL [10 to 12 mmol/L]) glycemic control [7]. At 30 days, IIT did not affect mortality or number of ventilator-free days and resulted in more frequent episodes of severe hypoglycemia. However, the achieved target glucose level in the conventional group was lower than expected (114 mg/dL [6.3 mmol/L]), which may have limited the overall analysis. Although the optimal blood glucose level in critically ill children has not been well defined, these results suggest that, similar to adults, IIT is of no benefit and may be harmful when episodes of hypoglycemia are frequent. (See "Glycemic control and intensive insulin therapy in critical illness", section on 'Children'.)

Score to predict neurologic status following in-hospital cardiopulmonary resuscitation (January 2014)

The likelihood of neurologically favorable survival following in-hospital cardiac arrest has generally been estimated based on the clinical judgement of the treating physician(s). Based upon data from in-hospital cardiac arrests in the United States from 2007 to 2009, the GO-FAR score divides patients into four categories for the likelihood of survival with good neurologic function following cardiac arrest (table 1) [8]. In general, younger patients with normal baseline neurologic function and fewer medical comorbidities had a greater likelihood of good neurological outcome. While awaiting further studies to validate this approach, the GO-FAR score might best be used as an aid for patients and families to better understand the goals and likely outcomes of care. (See "Prognosis and outcomes following sudden cardiac arrest", section on 'GO-FAR score to predict neurologically intact survival'.)

Futile therapy in the ICU (November 2013)

In a study of specialists in five intensive care units (ICUs) in a US academic healthcare system, 20 percent of critically ill patients were perceived by their ICU physician as receiving therapy that was futile or probably futile [9]. This is similar to reports from Canada and Europe. Two-thirds of those perceived as receiving futile therapy died before hospital discharge and the remaining one-third died in the subsequent six months or remained in a severely compromised state of health, indicating that these perceptions were accurate. Care that is perceived to be futile is associated with significant cost, delayed palliative care to relieve patient suffering, and physician burnout. Good communication with staff and family members and conflict resolution remain critical in managing requests for care that may be futile. (See "Ethics in the intensive care unit: Responding to requests for futile or potentially inappropriate therapies", section on 'Prevalence'.)

Statins in patients with ventilator-associated pneumonia (October 2013)

Some, but not all, studies have suggested that statin use might reduce the risk of infection, including pneumonia, and infection-related mortality. In a multicenter randomized trial to evaluate statin therapy in patients with ventilator-associated pneumonia, patients were assigned to either simvastatin or placebo, to be continued through intensive care unit (ICU) discharge or up to 28 days [10]. The trial was stopped early for futility. After enrollment of 300 patients, day 28 mortality was not lower in the statin group compared with the placebo group (21 versus 15 percent). There were also no significant differences in day 14, ICU, or in-hospital mortality rates; duration of mechanical ventilation; or changes in Sequential Organ Failure Assessment (SOFA) score. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Lack of benefit of statins'.)

Crystalloids versus colloids for hypovolemic shock (October 2013)

In patients with hypovolemic shock not due to bleeding, resuscitation with colloid-containing solutions has been associated with an increased need for renal replacement therapy and death. As a result, crystalloid solutions have become the preferred solution for resuscitation in this population. This practice was challenged by an open-label, multicenter, nine-year, randomized trial (CRISTAL) that compared intravenous crystalloid or colloid solutions in nearly 3000 patients with hypovolemic shock and found no difference between the groups in 28-day mortality or need for renal replacement therapy. In addition, patients treated with colloids had more days free of mechanical ventilation and vasopressor therapy as well as a lower 90-day mortality [11]. However, the open-label design, lengthy study period, and heterogeneity of fluids used limits confidence in the findings. Validation of any potential benefit of colloids will be required before they can replace crystalloids as the preferred therapy for the resuscitation of patients with hypovolemic shock not due to bleeding. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Overview'.)

Beta blockade as a therapy in septic shock (October 2013)

Beta blockade may have potential benefit in limiting harmful effects associated with the adrenergic surge that occurs in patients with sepsis. An open-label, single center trial randomized 154 patients with septic shock to an infusion of esmolol (short-acting beta blocker) or standard therapy [12]. All patients on esmolol achieved the pre-set target heart rate of 80 to 94 beats/min without a significant drop in mean arterial pressure. Compared to patients on standard therapy, patients receiving esmolol had improvements in left ventricular stroke work index, markers of end-organ function (eg, glomerular filtration rate), and a reduced need for vasopressors that were associated with a mortality benefit at 28 days. Further validation of these findings is warranted before esmolol can be routinely recommended as a therapy in patients with septic shock. (See "Investigational and ineffective therapies for sepsis", section on 'Beta-blockade'.)

Universal contact precautions in the intensive care unit (October 2013)

The issue of whether to use universal contact precautions for every patient in the intensive care unit (ICU), regardless of colonization history, is a matter of ongoing debate. Although this may be a reasonable practice in outbreak settings or institutions that have a high rate of colonization or infection with drug resistant bacteria, routine use of universal contact precautions is not yet supported by strong scientific evidence. In a large cluster randomized trial, universal gown and glove use did not reduce the primary combined endpoint of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin resistant enterococcus (VRE) acquisition more than gown and glove use only for known colonization or infection with drug resistant bacteria [13]. There were no excess adverse events with the use of universal contact precautions. (See "Epidemiology and prevention of infections and antimicrobial resistance in the intensive care unit", section on 'Contact precautions'.)

FDA approval of telavancin for HAP and VAP (October 2013)

Telavancin is an antibiotic with activity against methicillin-resistant Staphylococcus aureus. In 2013, telavancin was approved by the US Food and Drug Administration (FDA) for the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus, but not for other bacterial causes of HAP or VAP; it is recommended only when alternative agents cannot be used [14]. The FDA has included several boxed warnings for telavancin, which must be considered before choosing it [15]. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Telavancin'.)


Screening for lung cancer (January 2014)

The US Preventive Services Task Force (USPSTF) has revised its guidelines for screening for lung cancer, based on a systematic review and an analysis of the benefits and harms of lung cancer screening [16,17]. The USPSTF now recommends annual low-dose CT scan for high-risk adults (30 pack-year smoking history and current smoker or quit within the past 15 years), aged 55 to 80 years, with discontinuation of screening once the individual has not smoked for 15 years or has a limited life expectancy [18]. UpToDate authors support the USPSTF recommendations. Criteria for screening from several other groups vary slightly, setting 74 years as the upper age for screening, consistent with the study population in the National Lung Screening Trial. (See "Screening for lung cancer", section on 'Recommendations for screening by expert groups'.)


Thrombotic risk postpartum (February 2014)

In postpartum women, the risk of venous thrombosis is highest during the first six weeks, but less is known about when the risk returns to baseline. A five-year retrospective analysis of almost 1.7 million women examined rates of thrombosis during the first year following delivery, comparing various postpartum time periods to a six-week period one year later [19]. Risk of a thrombotic event was 11 times higher in the first six weeks postpartum (25 per 100,000 deliveries) and abruptly declined by 7 to 12 weeks (6 per 100,000 deliveries), returning to baseline by 13 to 18 weeks (2 per 100,000). Thus, the risk of thrombosis postpartum persisted beyond six weeks but absolute rates were low in weeks 7 to 18. These results support current practice of postpartum thromboembolism prophylaxis in select populations for a minimum of six weeks with extended prophylaxis for longer periods in those at higher risk. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Timing during pregnancy'.)

Catheter-directed thrombolysis for pulmonary embolism (January 2014)

The systemic administration of thrombolytic agents for acute pulmonary embolism (PE) carries an important risk of bleeding. To reduce this risk, thrombolytic agents can be delivered via an indwelling pulmonary artery catheter, resulting in lower systemic doses and more rapid clot lysis, and ultrasound therapy can be simultaneously applied via the catheter to encourage clot fragmentation. A randomized trial in 59 patients with acute intermediate-risk PE found that ultrasound-assisted catheter-directed thrombolysis (USAT) reduced right ventricular size at 24 hours compared with intravenous heparin alone [20]. There were no significant differences in mortality or major bleeding events between the groups at 90 days. Further randomized trials are needed that evaluate clinically meaningful outcomes and assess the populations most likely to benefit from this approach before USAT can be recommended for routine use in the treatment of PE. (See "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis", section on 'Catheter-directed'.)

Graduated compression stockings for the prevention of post thrombotic syndrome (December 2013)

Small randomized trials of patients with acute deep venous thrombosis (DVT) have suggested that graduated compression stockings (GCS) reduce the occurrence of post thrombotic syndrome (PTS) by up to 50 percent. However, in a new larger randomized trial of over 800 patients with first proximal DVT, use of GCS resulted in no difference in the rate of PTS [21]. Thus, available data are conflicting and do not support the routine application of GCS in patients following a first episode of acute DVT for the prevention of PTS, although GCS may be used for patients who are not adverse to their inconveniences and in whom the risk of PTS is considered high. (See "Treatment of lower extremity deep vein thrombosis", section on 'Ambulation and compression stockings'.)

Risk of venous thromboembolism in women hospitalized during pregnancy (December 2013)

The risk of venous thromboembolism (VTE) in pregnant women who are hospitalized for non-delivery reasons is not well defined, although acute admission to the hospital and pregnancy are both independent risk factors. The risk of first VTE was assessed in an analysis of over 200,000 women who had one or more pregnancies over a 13-year period [22]. Admission to the hospital for non-delivery reasons was associated with an 18-fold higher rate of VTE during hospitalization and 6-fold higher rate during the 28 days after discharge, compared to rates while not hospitalized. The highest rates were observed in those with a BMI >30 kg/m2, maternal age >35 years, admission during the third trimester, and a hospital stay >3 days. Although this level of risk is similar to that of hospitalized patients in the general population for whom thromboprophylaxis is frequently prescribed, further study is needed to define the safety and efficacy of thromboprophylaxis in hospitalized pregnant women before intervention can be routinely recommended. (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention", section on 'Antepartum admission'.)

Genotyping ineffective for improving warfarin initial dosing (November 2013)

Initial dosing of vitamin K antagonists (eg, warfarin) is uncertain; pharmacokinetics can be affected by polymorphisms in genes that control drug or clotting factor metabolism. Three trials evaluated the role of genotyping in determining the initial drug dose by randomizing patients to clinically-based dosing or dosing based on genotype [23-25]. The time in the therapeutic INR range, a surrogate for efficacy and adverse events, was unaffected by genotype-based dosing in two trials and minimally improved in the third. Overall bleeding rates were similar between arms in all three trials. Thus, we do not use genotyping to guide vitamin K antagonist initial dosing in routine clinical practice. (See "Therapeutic use of warfarin and other vitamin K antagonists", section on 'Use of genotyping'.)


Pregabalin versus pramipexole for the treatment of restless legs syndrome (February 2014)

Two major classes of drugs are used to treat restless legs syndrome (RLS) in adults: dopamine agonists and alpha-2-delta calcium channel ligands. Both classes have been shown to be effective compared with placebo, but the classes have not been compared head-to-head. In a randomized trial that included over 700 adults with RLS, both pregabalin and pramipexole reduced the symptom burden of RLS more than placebo but augmentation, a complication of dopaminergic therapy that can limit long-term effectiveness, occurred less frequently with pregabalin [26]. Overall, however, pregabalin was less well tolerated than pramipexole, leading to a higher rate of treatment discontinuation due to side effects. More comparative trials are needed to better understand the long-term safety and tolerability profile of treatment options for RLS. (See "Treatment of restless legs syndrome in adults", section on 'Pregabalin'.)

Hypoglossal nerve stimulation for obstructive sleep apnea (January 2014)

Hypoglossal nerve stimulation via an implantable neurostimulator is a novel treatment strategy for patients with obstructive sleep apnea (OSA). In the largest study to date, 126 patients with moderate to severe OSA who had difficulty accepting or adhering to continuous positive airway pressure (CPAP) therapy underwent surgical placement of a hypoglossal nerve stimulator [27]. One year after implantation, the mean apnea hypopnea index decreased from 29 to 9 events per hour in treated patients. The device is not yet available clinically but may emerge as a treatment option in patients who fail CPAP therapy. (See "Management of obstructive sleep apnea in adults", section on 'Hypoglossal nerve stimulation'.)


Acid suppression and pneumonia (March 2014)

Previous observational studies reported an association between proton pump inhibitor (PPI) use and community acquired pneumonia (CAP), but a new meta-analysis suggests the observation might have been due to confounding. The meta-analysis included eight cohort studies with over 4 million new users of nonsteroidal antiinflammatory drugs (NSAIDs), of which nearly 100,000 were treated prophylactically with PPIs and about 50,000 were treated with histamine 2 receptor antagonists (H2RAs) [28]. On adjusted analysis, neither the use of PPIs nor H2RAs was associated with an increased risk of hospitalization for CAP during the six months following initiation of NSAIDs. (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Pneumonia'.)

A new genetic cause of recurrent respiratory infections and bronchiectasis (January 2014)

A new genetic defect has been identified that causes a primary immunodeficiency (PID) associated with recurrent respiratory tract infections and bronchiectasis. This dominant gain-of-function point mutation in the catalytic subunit (p110δ) of phosphoinositide 3-kinase delta (PI3Kδ) causes increased production of phosphatidylinositol 3,4,5-trisphosphate (PIP3), leading to defective T and B cell function [29]. Activated PI3K-delta syndrome (APDS) was found in 17 patients from 7 unrelated families, suggesting that it is a relatively common PID in patients with this clinical presentation. Patient are treated with immune globulin replacement therapy and antibiotics. Selective p110δ inhibitors are a possible alternative therapeutic approach. (See "Combined immunodeficiencies", section on 'Activated PI3K-delta syndrome (APDS)'.)

ACIP recommendations for seasonal influenza vaccination (September 2013)

The United States Advisory Committee on Immunization Practices (ACIP) has published recommendations for seasonal influenza vaccination for the 2013 to 2014 influenza season [30]. As in past years, all individuals six months of age or older should be vaccinated. Both trivalent and quadrivalent vaccines are available for the 2013 to 2014 influenza season (table 2). New vaccines include a trivalent inactivated influenza vaccine produced in cultured mammalian cells (Flucelvax) and a trivalent recombinant hemagglutinin influenza vaccine (Flublok). The choice of vaccine formulation depends upon several factors, including age, comorbidities, pregnancy, and risk of adverse reactions. (See "Seasonal influenza vaccination in adults", section on 'Antigenic composition' and "Seasonal influenza vaccination in adults", section on 'Vaccine formulations' and "Seasonal influenza vaccination in children", section on 'Choice of vaccine'.)

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