Recent Research

Smoking cessation before surgery, dalteparin versus unfractionated heparin, and more.

Smoking cessation soon before surgery may not affect outcomes

Patients who stop smoking shortly before scheduled surgery may not have worse outcomes because of it, according to a recent study.

Previous studies have indicated that patients who stop smoking within eight weeks before surgery have worse postoperative outcomes than those who continue smoking. Researchers in London performed a systematic review and meta-analysis to compare postoperative outcomes in patients who continued smoking and those who quit shortly before surgery. Included studies allowed researchers to compare postoperative complications in surgical patients who stopped smoking within eight weeks before surgery and those who did not. The results were published in the June 13 Archives of Internal Medicine.

Nine studies involving 889 patients were included in the meta-analysis. Recent quitting was associated with a beneficial effect on outcomes compared with continued smoking in one study. Quitting smoking eight weeks before surgery had no positive or negative effect on postoperative complications compared to not quitting in meta-analyses of all studies (relative risk [RR], 0.78; 95% CI, 0.57 to 1.07), three high-quality studies (RR, 0.57; 95% CI, 0.16 to 2.01) or four studies that assessed pulmonary complications (RR, 1.18; 95% CI, 0.95 to 1.46).

The authors pointed out that their results are based on observational data and encompassed several types of studies, among other limitations, and as such should be considered “tentative.” However, they concluded that according to available data, smoking cessation shortly before surgery does not negatively affect postoperative outcomes. Patients should be counseled to stop smoking as soon as possible, but no evidence suggests that physicians should not encourage them to quit within a few weeks of surgery, the authors wrote. They called for larger studies to assess the question and provide more definitive data.

An accompanying commentary agreed that the study was limited and did not give a firm answer about the optimal time for smoking cessation before surgery. “It is questionable whether clinicians should be reassured that the timing of smoking cessation prior to surgery does not matter,” the commentary authors wrote. “Physicians should ideally try to get their patients to stop smoking several months prior to their surgery. The appropriate advice regarding the optimal time of smoking cessation for patients seen close to their scheduled surgery awaits further research.”

Dalteparin not superior to unfractionated heparin for preventing proximal DVT in the critically ill

The low-molecular-weight heparin dalteparin was not superior to unfractionated heparin for preventing proximal leg deep venous thrombosis (DVT) in critically ill patients, but the dalteparin group did have a secondary outcome of fewer pulmonary emboli, a recent study found.

Researchers performed a randomized, multicenter trial to determine whether low-molecular-weight heparin would outperform unfractionated heparin for thromboprophylaxis against proximal DVT. A total of 3,746 patients in intensive care units were randomly assigned to receive subcutaneous dalteparin, 5,000 IU once daily plus placebo once daily, or unfractionated heparin, 5,000 IU twice daily. The primary outcome was proximal leg DVT on compression ultrasonography performed within two days after admission, twice per week, and when clinically indicated. The secondary outcomes were any DVT, pulmonary embolism, venous thromboembolism (VTE), death, a composite of VTE or death, major bleeding, and heparin-induced thrombocytopenia. The study results were published in the April 7 New England Journal of Medicine.

Eligible patients were at least 18 years old, weighed at least 45 kg (99 lb) and had an expected intensive care unit stay of at least three days. Of the 3,746 patients, 1,873 were randomly assigned to receive dalteparin and 1,873 were randomly assigned to receive unfractionated heparin. In intention-to-treat analysis, the rate of proximal leg DVT did not differ between the dalteparin group and the unfractionated heparin group (5.1% vs. 5.8%). The hazard ratio for the dalteparin group was 0.92 (95% CI, 0.68 to 1.23; P=0.57). Patients in the dalteparin group had a significantly lower rate of pulmonary embolism than those in the unfractionated heparin group (1.3% vs. 2.3%; hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P=0.01), as well as a lower rate of heparin-induced thrombocytopenia (0.3% vs. 0.6%; hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P=0.046). Rates of major bleeding and in-hospital death did not significantly differ.

The authors noted that their results were limited by their use of screening compression ultrasonography to detect DVT, and noted that they might have had different findings if more patients had been enrolled or different drug regimens had been used. They concluded that in this study of critically ill medical and surgical patients, the low-molecular-weight heparin dalteparin was not superior to unfractionated heparin for preventing proximal DVT. Although patients receiving dalteparin were significantly less likely to develop pulmonary embolism, this finding was not accompanied by a corresponding significant decrease in the rate of proximal DVT. Possible explanations, according to the authors, include embolism from other sites, an effect of dalteparin on the propensity of leg thrombi to embolize, new-onset thrombus formation in pulmonary arteries during critical illness, and insensitivity or nonspecificity of proximal ultrasonography in asymptomatic patients.

Intravenous stroke thrombolysis can be given seven weeks after MI

Intravenous stroke thrombolysis may be given as early as seven weeks after myocardial infarction (MI), instead of three months post-MI as current guidelines say, a recent literature review suggested.

Many current guidelines list MI within three months as a contraindication to stroke thrombolysis, including the American Heart Association/American Stroke association guidelines. Most clinical trials of IV altepase for stroke thrombolysis, including the National Institute of Neurological Disorders and Stroke trial, also excluded patients with MI in the prior three months. Researchers thus reviewed the published literature on the subject, via PubMed and Ovid searches, and by manually searching references for randomized controlled trials and guidelines on IV thrombolysis for stroke and MI. Results were published in the May 24 Neurology.

There is a distinct lack of data, the researchers wrote, adding that they found only five thrombolyzed stroke patients with recent MI who were reported to have had cardiac tamponade. Indirect histopathologic evidence suggests the risk associated with IV thrombolysis after MI is highest within seven weeks of the MI, they wrote. After seven weeks, the risk for cardiac rupture can be stratified, and IV thrombolysis may be considered for patients younger than 62 years who don't have transmural involvement, they said. The risk of cardiac rupture should be weighed against the implications of withholding thrombolysis, the researchers advised. In general, they added, there is “no evidence” supporting a three-month time window for MI as a contraindication to IV stroke thrombolysis.

The lack of data on complications of IV stroke thrombolysis after MI could be due to underreporting, or it could be that the risk is actually low, the authors noted. They proposed creating a registry of thrombolyzed and nonthrombolyzed stroke patients with recent MI to document incidence and risk factors for cardiac rupture, and ultimately to develop evidence-based guidelines.

D-dimer testing may help rule out acute aortic dissection

Plasma d-dimer testing may be helpful in determining which patients do not have acute aortic dissection, according to a recent meta-analysis.

Researchers performed a meta-analysis of seven studies involving 298 patients with acute aortic dissection and 436 without to determine whether testing plasma d-dimer (DD) could help clinicians rule out acute aortic dissection. Included studies reported acute aortic dissection confirmed by standard imaging within two weeks of symptom onset; measured plasma DD with standardized assays; included controls without acute aortic dissection; and provided absolute true-positives, false-positives, true-negatives, and false-negatives, or enough data to allow these numbers to be derived. Each study included 16 to 94 patients with acute aortic dissection, with a mean/median age of 53 to 70 years, most of whom were men. The study results were published in the April 15 American Journal of Cardiology.

The study authors used a threshold of 500 ng/mL as a positive DD finding. Data were pooled across studies, and sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were estimated. Sensitivity and negative predictive value were both high (0.97 [95% CI, 0.94 to 0.99] and 0.96 [95% CI, 0.93 to 0.98], respectively), while specificity and positive predictive value were both low (0.56 [95% CI, 0.51 to 0.60] and 0.60 [95% CI, 0.55 to 0.66], respectively). Discriminative ability was excellent with negative likelihood ratio but not with positive likelihood ratio (0.06 [95% CI, 0.03 to 0.12] and 2.43 [95% CI, 1.89 to 3.12], respectively).

The meta-analysis could not examine DD's diagnostic performance in different settings, and the results may be more applicable to patients at low and moderate risk than to those at high risk, the authors noted. They also pointed out that since acute aortic dissection has a high mortality rate, it may be dangerous to forgo further imaging based on a negative DD value in situations where the value has not been adequately tested, such as certain age ranges. Finally, they acknowledged that all of the included studies were observational. However, they concluded, “Use of this screening tool may help physicians decide whether to order additional diagnostic procedures to confirm the diagnosis of [acute aortic dissection].” They called for additional prospective studies to quantify the utility of DD testing in a variety of clinical settings.

Readmissions difficult to predict

Neither providers nor an algorithm accurately predicted which patients had the highest risk of readmission, a recent study found.

Researchers used the electronic medical record at the University of California, San Francisco Medical Center to screen general medicine admissions for eligible patients, and to identify readmissions. Phone calls were also used for the latter. Study patients comprised 164 adults at least 65 years old who were discharged from the general medicine service. Provider subjects included 24 attending physicians, 42 housestaff physicians, six case managers and more than 30 nurses. At discharge, providers estimated a patient's chance of unscheduled readmission within 30 days and predicted the reason for possible readmission. Researchers also calculated the Probability of Repeat Admission (Pra) for each patient. The Pra is an algorithm for predicting the probability of at least two hospital readmissions during a four-year period, based on eight risk factors including age, self-rated health, and prior hospital admission in the past year. Results were published in the July Journal of General Internal Medicine.

Five enrolled patients died within 30 days of discharge. Of the remaining patients, 32.7% (n=52) were readmitted, and 4.4% (n=7) presented to the emergency department but weren't readmitted. Mean readmission predictions by physicians were closest to the actual rates (attendings, 33.0%; residents, 30.0%; interns, 31.5%). Readmissions were overestimated by the Pra (41.5%), nurses (43.5%) and case managers (39.0%). The P value was less than 0.05 for the comparison of nurses, case managers and the algorithm with the actual readmission rate. By receiver-operating characteristic curves, the ability to discriminate between readmissions and nonreadmissions was poor for all provider groups and for the Pra (AUC of 0.50 for nurses, 0.56 for Pra and 0.59 for interns). Discriminatory ability was best for the intern physician group, followed by attending and resident physicians and the Pra, but these findings weren't statistically different from 0.50 (i.e., chance). No provider group accurately predicted the reasons for readmission (i.e., predicted the correct or a related diagnosis more than 51% of the time); nurses and interns had the highest accuracy. All groups underestimated the degree to which patients would be readmitted for adverse effects of therapy.

The readmission rate in this study is significantly higher than the 19.6% readmission rate seen in a 2009 New England Journal of Medicine study of nearly 12 million Medicare patients, the authors noted, possibly because the current study involved tertiary care patients in an urban setting. The inability of providers to predict readmissions defied the researchers' original hypothesis that experience would make the providers ideal for the task, they wrote. Each provider has a unique viewpoint on the patient; it's possible the predictions may have been more accurate had all providers collaborated, the authors theorized. Possible reasons for poor predictions include the heterogeneity of general medicine patients; overlooked elements that factor into readmission like complications from treatment, including adverse drug events; and influences like processes of care during hospitalization and post-discharge care. Given this study's findings that readmission is common and unpredictable, the proposed changes for public reporting and reimbursement for readmissions leave hospitals “to struggle without guidance to aim their efforts” to reduce readmissions, the authors wrote.

Unfractionated heparin may be misprescribed in obese VTE patients

Obese patients may not receive correct weight-based doses of unfractionated heparin for venous thromboembolism (VTE), according to a single-site study.

Although risk for recurrent VTE is higher in obese patients, physicians may be reluctant to base unfractionated heparin doses on weight because of fear of increased bleeding. Researchers at an academic teaching hospital in New York performed a cross-sectional consecutive case series over three years to examine the use of unfractionated heparin in obese patients with VTE. Included patients had a BMI of at least 30 kg/m2 and received continuous unfractionated heparin for pulmonary embolism or deep venous thrombosis between Jan. 1, 2004 and Dec. 31, 2006. The study results appeared in the May Journal of General Internal Medicine.

Eighty-four patients were included in the study. Twenty-nine percent achieved therapeutic coagulation (defined as an activated partial thromboplastin time >60 seconds) after more than 24 hours, and 14% achieved it after more than 48 hours. Prescribed bolus doses were lower than the recommended dose of 80 units/kg in 89% of patients, and the initial continuous infusion was more than 100 units/h below the recommended dose of 18 units/kg per hour in 76% of patients. Physicians prescribed an infusion of 1,000 units/h regardless of body weight in 28.6% of patients. Initial infusion dose was significantly related to time to achieving therapeutic anticoagulation (Spearman r=−0.27; P<0.02).

The researchers pointed out that their study was small and did not include follow-up data after discharge. However, they concluded that physicians often do not follow weight-based dosing guidelines when prescribing unfractionated heparin for VTE in obese patients. In the current study, this led to a delay in therapeutic anticoagulation and inadequate bolus doses and/or initial therapeutic infusion. “Since obese patients already face an elevated risk of recurrence, it is especially important for physicians to avoid overcautious behavior and, instead, to administer aggressive anticoagulation therapy to help protect these VTE patients from adverse outcomes,” the authors wrote.

Fewer calories better for some mechanically ventilated patients

Initial low-volume enteral nutrition is associated with fewer episodes of gastrointestinal intolerance than full-energy enteral nutrition among mechanically ventilated patients with acute respiratory failure, and it doesn't harm outcomes, a study found.

In a randomized, open-label study, researchers enrolled 200 patients from two ICUs at a single academic center who were expected to require mechanical ventilation for at least 72 hours and whose primary team intended to initiate or continue enteral nutrition. Patients were randomized to either initial full-energy enteral nutrition (n=102) or initial trophic enteral nutrition (n=98) for six days followed by advancement to full-energy enteral nutrition. Patients in the full-energy group had enteral nutrition initiated at 25 mL/h, with the feeding rate increased by 25 mL/h every six hours until the full-energy feeding rate was achieved. Full-energy feeding rates targeted 25 to 30 kcal/kg of predicted body weight per day of nonprotein energy and 1.2 to 1.6 g/kg of predicted body weight per day of protein. Trophic group patients had enteral nutrition initiated at 10 mL/h. In patients still ventilated at 144 hours, enteral nutrition was advanced to full-energy target feeding rates using the same protocol as for the full-energy feeding group. The primary outcome measure was ventilator-free days to day 28.

The patient groups didn't differ in number of ventilator-free days (median, 23 days; P=0.90), intensive-care-unit-free days (median, 21 days; P=0.64), or mortality to hospital discharge (22.4% for the trophic group vs. 19.6% for the full-energy group; P=0.62). In the first six days, the trophic group had significantly fewer episodes of elevated gastric residual volumes (2% vs. 8% of feeding days; P<0.001) and trends for less diarrhea (19% vs. 24% of feeding days; P=0.08). Both groups received similar durations of enteral nutrition, about five to five-and-a-half days. The trophic group received an average of 15.8% ± 11% of goal calories daily through day six compared to 74.8% ± 38.5% (P< 0.001) for the full-energy group. Results were published in the May Critical Care Medicine.

Consensus guidelines recommend enteral over parenteral nutrition in patients with acute respiratory failure who cannot eat by mouth, and recommend advancing enteral nutrition to full-energy rates over the first 48 to 72 hours. Yet this trial shows that providing trophic enteral nutrition for the first six days leads to similar outcomes as advancing quickly to full-energy rates, while reducing gastrointestinal intolerance. Larger studies are needed to determine the risks and benefits, as well as the optimal composition and timing of starting enteral nutrition in these patients, and to clarify whether supplementation with protein or micronutrients is beneficial, the authors concluded.

Asthma pill as effective in real world as glucocorticoids, LABAs

Leukotriene-receptor antagonists showed little difference in real-world effectiveness, and had better adherence, compared to more commonly recommended treatments, according to a report of two pragmatic trials.

The first of the trials included 300 British primary care patients between 12 and 80 years old who had inadequate asthma control or impaired asthma-related quality of life. The patients were randomly assigned to two years of open-label therapy with either a leukotriene-receptor antagonist (LTRA) or an inhaled glucocorticoid as their first-line asthma therapy. The second trial included 350 similar patients who were already taking an inhaled glucocorticoid as first-line therapy, and they were randomized to either an LTRA or a long-acting beta-agonist (LABA) as add-on therapy. The groups' scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were compared during the following two years of open-label treatment.

Overall, mean MiniAQLQ scores increased during the two years. After two months of treatment, scores were equivalent between patients taking LTRA or other drugs in both trials. After two years of treatment, the scores were almost equivalent, but they did not meet the study authors' pre-specified, and intentionally conservative, criterion for equivalence (mean difference between groups, −0.11), with the other drugs slightly outperforming LTRAs.

Adherence to an LTRA was better than to the other drugs (numerically better at 65% vs. 41% [P=0.11] for the first trial, and statistically better at 74% vs. 46% [P=0.007] for the second), probably because it's easier to take a pill than use an inhaler, noted an accompanying editorial. The editorialist noted other advantages to LTRAs, including their effects on comorbidities such as rhinitis and ease of use in the developing world. The trials and editorial appeared in the May 5 New England Journal of Medicine.

The study authors urged caution in interpreting their results, since the trials were limited by lack of a placebo control and crossover between treatment groups. However, the pragmatic trial design did allow analysis of adherence, as well as inclusion of patients who would typically be excluded from such research. Almost a quarter of the studied patients were smokers, and 3% may have had COPD, making them more like real-world patients than typical study populations.

Linezolid not superior to glycopeptides for MRSA pneumonia

Commonly used drug linezolid is not superior to vancomycin or teicoplanin in treating suspected methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, a meta-analysis found.

Researchers conducted a systematic review and meta-analysis of randomized, controlled trials that compared use of linezolid to glycopeptide antibiotics for suspected MRSA pneumonia in patients 13 years and older. They identified studies by searching PubMed's MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL). Trials were excluded from the analysis if they weren't in English, didn't assess clinical success as an end point, and studied strictly immunocompromised subjects. Of 762 articles retrieved, eight met entry criteria and were selected for meta-analysis; they included a total of 1,641 patients, all hospitalized. All trials were multi-center and half were double-blind. Two studies investigated teicoplanin as the comparator medication; the other six studied vancomycin. All studies used linezolid doses of 600 mg IV every 12 hours and allowed use of concomitant antibiotics with gram-negative, but not MRSA, activity. Results were published in the May Chest.

Linezolid was not superior to the glycopeptides in terms of clinical success (P=0.28), microbiologic success (P=0.12), mortality (P=0.47) or total adverse events (P=0.48). Clinical success in the subgroup of subjects with MRSA-positive respiratory tract culture also was not significantly different from those without MRSA. Risk for thrombocytopenia was a nonstatistically significant 2.97 times higher for linezolid (P=0.10) in three studies reporting this data; risk of renal impairment was not significantly different (P=0.89)

MRSA is the most common pathogen associated with nosocomial pneumonia, and societal guidelines suggest linezolid may be the preferred treatment for it, yet this meta-analysis doesn't support its superiority to glycopeptide antibiotic, the authors noted. The results are consistent with other meta-analyses comparing these two types of drugs for treating multiple sources of infection, they noted. Several studies have investigated the cost-effectiveness of linezolid for MRSA pneumonia and concluded that, although it costs about 10 times more than vancomycin, it is cost-effective in light of assumed improved outcomes—a conclusion that should be reassessed in light of the current analysis, the authors said. Decisions about the use of linezolid or glycopeptides for empirical or MRSA-directed therapy of nosocomial pneumonia should be based on “local availability, antibiotic resistance patterns, preferred routes of delivery, and cost, rather than presumed difference in efficacy,” the authors concluded.