Recent Research

ICU glycemic control adoption, beta-blockers at discharge, cognitive function after cardiac arrest, and more.

ICUs were faster to adopt tight glycemic control than to deadopt it

Glycemic control gradually tightened in U.S. ICUs after the publication of a trial supporting tight control, but practice changed little when a subsequent trial found harm from tight control, a recent study noted.

To assess the practice impact of the 2001 van den Berghe trial, which supported tight glycemic control, and the 2009 NICE-SUGAR trial, which found higher mortality with tight control, researchers conducted an interrupted time-series analysis of more than 300,000 patients treated in 113 ICUs between 2001 and 2012. Results were published in the May JAMA Internal Medicine.

Before publication of either trial, 17.2% of patients had tightly controlled glucose on day 1 of ICU admission (between 80-110 mg/dL), while 3% had hypoglycemia (<70 mg/dL), and 40.2% had hyperglycemia (≥180 mg/dL). After publication of the first trial, the percentage of patients with tight control gradually increased (1.7% per quarter) as did the rate of hypoglycemia (2.5% per quarter), while hyperglycemia dropped (−0.6% per quarter). After the NICE-SUGAR trial was published, there was an immediate drop in hypoglycemia (−22% in the first quarter), but no subsequent change, and there was no change in rates of tight glycemic control or hyperglycemia.

The study authors concluded that publication of evidence for tight glycemic control led to slow steady adoption of this practice but that the later evidence of harm from tight glycemic control resulted in little deadoption. The findings show the importance of seeking confirmatory research before implementation of a practice and observing new practices for potential harms. “There is an urgent need to understand and promote the deadoption of ineffective clinical practices,” wrote the authors.

An accompanying commentary agreed on the need for a model of deadoption or undiffusion, which lacks even an agreed-upon name, the commentary author noted. This study and others on the topic (published in the same issue of the journal) show that “it will often be prudent to phase in an innovation practice gradually, waiting whenever possible for reports of real-world effectiveness studies and syntheses of multiple well-conducted controlled studies in systematic reviews or meta-analyses,” the commentary said.

Beta-blockers at discharge associated with lower mortality in COPD plus MI

Patients with chronic obstructive pulmonary disease (COPD) had lower mortality after myocardial infarction (MI) if they were discharged on beta-blockers, a recent Swedish study found.

The retrospective cohort study included 4,858 Swedish patients with COPD who were hospitalized for MI between 2005 and 2010 and survived to discharge. They were followed for a maximum of 7.2 years. Results were published by the Journal of the American Heart Association on April 8.

Beta-blockers were prescribed at discharge to 84.1% of the COPD patients, with the other 15.9% of patients not receiving a prescription. After adjustment for comorbidities and other confounders, the study found a significantly reduced mortality risk in the patients receiving beta-blockers (hazard ratio [HR], 0.87; 95% CI, 0.78 to 0.98). Patients who also had heart failure showed an even greater reduction in risk with beta-blockers (HR, 0.77; 95% CI, 0.63 to 0.95).

The patients who didn't receive beta-blockers were older, more likely to have a history of stroke or heart failure, and less likely to have hypertension, the study authors noted. They were also more likely to be prescribed calcium-channel blockers and diuretics and took more COPD medications at baseline. They had less invasive treatment during hospitalization and received less treatment with secondary prevention agents other than beta-blockers.

The results suggest that MI patients with COPD may benefit from beta-blockers, the study authors concluded. The possibility of underuse of these drugs in COPD patients, especially those with heart failure, is problematic, but this observational study could not definitively determine whether patients had unmeasured contraindications to beta-blockers or were truly being undertreated, the authors said. The study was also limited by lack of data on whether patients started or discontinued beta-blockers at some point after discharge.

Cognitive function after cardiac arrest similar with different temperature strategies

Cardiac arrest patients treated to a target temperature of 33 °C or 36 °C had similar long-term cognitive function, with almost two-thirds of survivors reporting a complete mental recovery, a recent study found.

The Targeted Temperature Management (TTM) trial randomized more than 900 European and Australian patients who had out-of-hospital cardiac arrest in 2010 to 2013 to a targeted temperature regimen at either 33 °C or 36 °C. This study assessed their cognitive function and quality of life at 6 months. Results were published by JAMA Neurology on April 6.

The 2 temperature groups had similar median scores on the Mini-Mental State Examination (MMSE) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in an intent-to-treat analysis that included nonsurvivors (MMSE, 14 in the 33 °C group vs. 17 in the 36 °C group, P=0.77; IQCODE, 115 in both groups, P=0.57). Among survivors at 6 months, the median MMSE score (28 in both temperature groups, P=0.61) was in the reference range, and the median IQCODE scores were in the minor defect range (79.5 in the 33 °C group vs. 80.7 in the 36 °C group, P=0.04).

Of the survivors, 18.8% in the 33 °C group and 17.5% in the 36 °C group reported needing help with everyday activities, while 66.5% and 61.8%, respectively, reported that they thought they had made a complete mental recovery (P=0.32). The results showed that quality of life was good in most of these patients and similar between the 2 temperature groups, the study authors concluded, noting that “improved survival [from cardiac arrest] has not been accompanied by an increase in survivors with severe neurologic deficits.”

The initial TTM trial found no significant difference in neurologic function associated with the different temperatures, and this study didn't find either target superior on cognitive or quality-of-life outcomes, suggesting that lower temperatures may not improve cognitive function, an accompanying editorial said. It's possible that certain subgroups may see benefit from a specific temperature, but for now, the take-home message is that overall long-term outcomes in these patients are good, the editorialists concluded.

Beta-lactam monotherapy for CAP associated with similar mortality as broader strategies

Patients admitted with community-acquired pneumonia (CAP) and treated with an empirical strategy of beta-lactam monotherapy had similar outcomes as those treated with broader-spectrum strategies, a recent study found.

The cluster-randomized crossover trial included more than 2,000 Dutch patients admitted to non-ICU hospital wards with CAP. Three treatment strategies—beta-lactam monotherapy, beta-lactam-macrolide combination therapy, and fluoroquinolone monotherapy—were rotated in 4-month periods. Patients' median age was 70. Results were published in the April 2 New England Journal of Medicine.

Adherence to the strategy was 93.0% with beta-lactam monotherapy, 88.0% with beta-lactam-macrolide combination, and 92.7% with fluoroquinolones. Crude 90-day mortality rates were 9.0%, 11.1%, and 8.8%, respectively, under the 3 strategies. In an intention-to-treat analysis, the combination therapy was associated with a risk of death 1.9 percentage points higher than the beta-lactam monotherapy strategy, and the fluoroquinolone strategy was associated with a mortality risk 0.6 percentage point lower than beta-lactam monotherapy. Median length of stay was 6 days for all strategies, and median time to starting oral treatment was 3 days with fluoroquinolones and 4 days with the other strategies.

For patients with CAP treated on non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to the other studied strategies, the authors concluded. Based on these findings, as well as other evidence of risks such as resistance and cardiac effects, “the addition of macrolides for empirical treatment of CAP should be reconsidered,” they wrote. Regional differences in microbes could limit generalizability of the findings, however, with higher incidence of Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus requiring adaptation of the strategies, for example.

This trial's design differed from that of previous ones on the topic and reflected real-world medical practice by comparing strategies, rather than drugs, and allowing deviations from the assigned strategy for medical reasons. Despite deviations, the beta-lactam monotherapy strategy was associated with a 67% reduction in empirical atypical coverage compared with the combination strategy and a 69% reduction compared to the fluoroquinolone strategy, the authors noted.

Tiered system set criteria for calling rapid-response or treating teams

A 2-tier system for activating a rapid-response team was associated with changes in the triggers leading to ICU admission and decreased ICU mortality among triggering patients in an Australian hospital.

The retrospective observational study included 1,564 ICU admissions occurring before (2006–2009) or after (2011–2013) the hospital switched to a 2-tier rapid-response system. Under the 2-tier system, certain criteria (for example, respiratory rate <5 or >30 breaths/min or heart rate <40 or >140 beats/min) would trigger the medical emergency team (MET), which included an ICU resident, an ICU nurse, and a medical resident. However, less severe triggers (such as respiratory rate 5-10 or 25-30 breaths/min or heart rate 40-50 or 120-140 beats/min) would get a first-tier clinical review by the patient's admitting team.

Overall, the rate of MET activations increased from 22 per 1,000 hospitalizations to 31 per 1,000 over the studied time period. Certain triggers increased as a proportion of MET activations leading to ICU admission: tachypnea (from 11% to 15%; P<0.0001) and hypotension (from 27% to 43%; P<0.0001). Others decreased under the new system: reduced level of consciousness (from 20% to 17%; P<0.0001) and clinical concern (from 18% to 9%; P<0.0001). The rate of admissions due to tachycardia, seizure, and cardiorespiratory arrest did not change.

ICU mortality for patients admitted after MET calls for tachypnea, tachycardia, and clinical concern decreased from 29% to 9% (P<0.0001), with no change in other triggers. The proportion of patients dying in the ICU with a do-not-resuscitate order was lower under the 2-tier system. These results suggested that the 2-tier system led to earlier recognition of reversible pathology or a decision not to escalate the level of care, the study authors concluded.

The authors noted that only about 10% of MET activations led to ICU admission, suggesting that the vast majority of patients are found stable enough to remain on the ward or not likely to benefit from ICU care. The 2-tier system may engage medical teams more actively in ward-based management of such patients. Because the study was single-center and retrospective, however, “caution is warranted when extrapolating the results,” the study authors said. The study was published in the April Critical Care Medicine.

ICUs vary in managing patients with treatment limitations

ICUs vary widely in their management of patients with preexisting limits on life-sustaining treatments, according to a recent study.

Researchers used the Project IMPACT database from April 1, 2001, to Dec. 31, 2008, to perform a retrospective cohort study examining the care received at ICUs by patients admitted with treatment limits. The main outcome measures were provision of cardiopulmonary resuscitation (CPR), provision of new forms of life support, and addition or reversal of treatment limitations. The study results were published online March 30 by JAMA Internal Medicine.

Overall, data from 141 ICUs and 277,693 ICU patient visits were examined. A total of 4.8% (95% CI, 4.7% to 4.9%) of ICU visits involved patients with previously established treatment limitations. The median age was 78 years, and 59.4% had dependent care needs at ICU admission. More than half (52.5%) were admitted to the ICU via the ED, and 77.4% entered the ICU with do-not-resuscitate (DNR) orders. Among patients whose treatment limitations included DNR orders, 24.6% (95% CI, 23.8% to 25.5%) received CPR and 15.7% (95% CI, 14.7% to 16.8%) of those who died received CPR.

Patients with treatment limitations who survived to hospital discharge were more likely to have existing treatment limitations reversed while in the ICU than they were to have new treatment limits added (17.8% [95% CI, 17.0% to 18.7%] vs. 11.7% [95% CI, 11.1% to 12.4%]; P<0.01). After adjusting for risk, the researchers found wide variations among ICUs in proportions of patients admitted with treatment limitations (range, <1% to 20.9%), proportions with treatment limitations who received CPR (range, 3.8% to 92.4%), proportions who received new forms of life-sustaining therapy (range, 6.0% to 84.2%), and proportions of survivors who had new treatment limits established (range, 1.9% to 57.3%) or reversed (range, 1.8% to 76.2%) during or after ICU admission. This variability did not appear to be related to center-level characteristics, the researchers found.

The researchers noted that they could not assess changes in patient care preferences during the ICU stay or changes in level of care before or after ICU admission, among other limitations. However, they concluded that patients who are admitted to ICUs in the United States with preexisting limits on treatment and survive to discharge are more likely to receive more aggressive than less aggressive care during the ICU stay.

“Many of these patients have favorable outcomes following ICU admission, but their care trajectories may be heavily influenced by the ICU in which they receive care,” the authors wrote. “By examining how treatment escalations and de-escalations are decided upon for this patient population at different ICUs, future research may identify targets for interventions that promote more patient-centered decision making.”

The authors of an accompanying editorial said that given these study results, clinicians should help patients and their families understand that ICU admission involves risk and may culminate in “the type of death patients with to avoid.” They recommended that hospital clinicians discuss benefits and risks of ICU admission with seriously ill patients and ensure that steps are taken to ensure the possibility of a “good death” for those who do choose the ICU.

“This might be achieved by mandating a goals-of-care conversation by skilled clinicians, such as palliative care consultants or specially trained hospitalists and intensivists,” the editorialists wrote. “Such conversations could increase the likelihood that the treatment plan supports the patient's best-laid plans and, if that involves admission to the ICU, ensure that both the family and the ICU team prepare for the worse, even while hoping for the best.”

Restrictive and liberal strategies have similar mortality and morbidity, review finds

Restrictive transfusion strategies were associated with similar rates of mortality, morbidity, and myocardial infarction as liberal strategies, a recent systematic review found.

The review included 31 published and unpublished trials with 9,813 patients (both adults and children) who were randomized to either a restrictive or liberal transfusion strategy. It found that patients treated with restricted strategies were less likely to receive red blood cells (relative risk, 0.54; 95% CI, 0.47 to 0.63; 24 trials) and received a lower number of red blood cell units (mean difference, −1.43; 95% CI, −2.01 to −0.86). The results were published by The BMJ on March 24.

The differing transfusion strategies weren't associated with any significant differences in mortality, overall morbidity, or fatal or nonfatal myocardial infarction, leading the study authors to conclude that restrictive strategies are safe in most clinical settings and that liberal strategies have not been shown to convey any benefit to patients. They noted that certain patient populations may require higher hemoglobin levels, such as those with coronary artery disease, particularly those with ongoing cardiac ischemia, or traumatic brain injury.

This analysis was limited by an overall low quality of evidence and widely differing trials, for example, some studies' liberal thresholds being equivalent to others' restrictive thresholds. The authors called for additional trials of liberal and restrictive transfusions in subpopulations but predicted that “it is unlikely that future trials will show overall harm with restrictive strategies.”

An accompanying editorial noted that “adverse effects from transfusion remain biologically plausible.” Blood transfusions have never been subjected to the scrutiny that new drugs and technologies undergo, and there is little cost-effectiveness data on the subject, so more research is needed, the editorialist wrote.

High rates of ICU admission for pneumonia associated with lower-quality care in elderly

High rates of ICU admission among elderly patients with pneumonia were associated with lower quality of care, a recent study showed.

Researchers conducted a retrospective cohort study in 2,812 U.S. hospitals to determine whether a relationship existed between ICU admission rates and care quality in elderly patients with pneumonia. Included patients were at least 65 years of age and were fee-for-service Medicare beneficiaries who in 2008 had a principal diagnosis of pneumonia or a principal diagnosis of sepsis or respiratory failure and a secondary diagnosis of pneumonia. Hospitals were organized by quintiles according to ICU admission rates for pneumonia. Rates of failure to deliver pneumonia processes of care, 30-day mortality, readmission to the hospital, and Medicare spending were compared across quintiles. The study results were published online March 10 by Critical Care Medicine.

The study involved a total of 551, 873 patients. ICU admission rates were below 17% in the lowest hospital quintile and ranged from 30% to 86% in the highest quintile. Five percent of hospitals had ICU admission rates above 41%. The researchers found that hospitals in the highest quintile of ICU admission rates were more likely to fail to deliver appropriate initial antibiotics (13.0% vs. 11.4%; P<0.001) and pneumococcal vaccination (15.3% vs. 13.4%; P=0.001) than hospitals in the other 4 quintiles. No significant association was seen between ICU admission rate quintile and influenza vaccination (19.8% vs. 18.0%; P=0.007) or blood culture before antibiotics (8.3% vs. 7.7%; P=0.08). Thirty-day mortality rates, 30-day hospital readmission rates, and hospital spending per patient were higher in the highest ICU admission quintile than in the other quintiles (P<0.001 for all comparisons).

The study could not measure severity of illness at hospital admission or time between hospital and ICU admission, and the results could be due to residual confounding, among other limitations, the authors noted. However, they concluded that hospitals with high ICU utilization for pneumonia may provide worse care according to process measures and may have higher mortality rates, costs, and readmission rates. “Researchers and policy makers should examine these poor performing hospitals to better understand why these deficiencies are occurring and develop interventions to improve the care delivered at these higher-cost hospitals,” the researchers concluded.

Sedative premedication before surgery may not improve patient experience, outcomes

Patients who receive sedative premedication with lorazepam before elective surgery involving general anesthesia may not benefit, according to a recent study.

Researchers performed a randomized clinical trial to determine the efficacy of sedative premedication before elective surgery with general anesthesia. Patients who were younger than age 70 and who were undergoing general surgery at 5 French teaching hospitals between January 2013 and June 2014 were randomly assigned to receive 2.5 mg of lorazepam, no premedication, or placebo. Patients who were undergoing neurosurgery or obstetric, cardiac, or outpatient surgery were excluded. The study's primary outcome was perioperative patient experience 24 hours after surgery, as assessed via a validated questionnaire, while secondary outcomes included time to extubation and early cognitive recovery. The study results were published in the March 3 Journal of the American Medical Association.

A total of 1,062 patients were included in the study, and 354 were randomly assigned to each study group. Three hundred thirty patients in the lorazepam group, 319 in the no premedication group, and 322 in the placebo group were included in the primary analysis. The researchers found that premedication with lorazepam did not improve the mean global index of overall patient satisfaction versus no medication or placebo (P=0.38). In addition, no significant difference was seen with lorazepam versus the other groups among the 24% of patients who had high preoperative anxiety (P=0.18). The lorazepam group had a time to extubation of 17 minutes, compared with 12 minutes in the no premedication group and 13 minutes in the placebo group (P<0.001). The rate of early cognitive recovery in the 3 groups, respectively, was 51%, 71%, and 64% (P<0.001).

The authors noted that their study examined only 1 premedication drug, that a class effect of the drug was probably present, and that the patients who received no medication were aware of that fact, among other limitations. They concluded that premedication with lorazepam before elective surgery involving general anesthesia did not improve the postoperative patient experience; however, they did find an association with modestly increased time to extubation and lower rates of early cognitive recovery. “The findings suggest a lack of benefit with routine use of lorazepam as sedative premedication in patients undergoing general anesthesia,” the authors wrote. They noted that since high preoperative anxiety is not seen in the majority of patients, “there is little justification for routine administration of preoperative anxiolytic medication for all surgical patients.”