Balanced crystalloids vs. saline, antibiotic stewardship, and more

Summaries from ACP Hospitalist Weekly.

Balanced crystalloids reduced kidney events compared to saline in two studies

Balanced crystalloids were associated with better kidney-related outcomes among hospitalized patients than saline, according to two studies conducted at a single academic medical center.

One study was conducted among 15,802 patients treated at any of five ICUs in the hospital. The multiple-crossover trial randomized the ICUs to give patients either saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A). The primary outcome was a composite of death from any cause, new renal-replacement therapy, or doubling of creatinine level from baseline, all before hospital discharge or 30 days. The composite outcome occurred in 14.3% of the balanced-crystalloid group compared to 15.4% of the saline group (marginal odds ratio [OR], 0.91 [95% CI, 0.84 to 0.99]; conditional OR, 0.90 [95% CI, 0.82 to 0.99]; P=0.04). In-hospital mortality was slightly lower in the balanced-crystalloid group (10.3% vs. 11.1%; P=0.06), as was incidence of new renal-replacement therapy (2.5% vs. 2.9%; P=0.08).

Image by Thinkstock
Image by Thinkstock

The second study included 13,347 patients who were treated with IV crystalloids in the ED and subsequently hospitalized outside an ICU. During the 16-month trial, the entire ED crossed over monthly between balanced crystalloids and saline. The median crystalloid volume administered in the ED was 1,079 mL. The primary outcome was days alive after discharge before day 28, while the secondary outcome was the same composite used in the ICU study. The primary outcome did not differ between the balanced-crystalloid and saline groups (median, 25 days in each group). However, the composite of death from any cause, new renal-replacement therapy, or doubling of creatinine level from baseline was significantly lower with balanced crystalloids than with saline (4.7% vs. 5.6%; adjusted OR, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

The results of the two studies are consistent with each other, the authors said, and although the observed effect sizes were modest, the widespread use of these IV fluids means that the benefits of balanced crystalloids could be substantial when extrapolated to a population level. However, they noted that the studies had several limitations, including that they were conducted at a single center, treating clinicians were unblinded, the balanced crystalloids were not compared against each other, and the non-ICU trial did not control for fluids administered after hospital admission.

An accompanying editorial said that the trials should inform clinicians' thinking about choice of resuscitation fluids but that the results should be interpreted cautiously. The editorialist noted that the composite outcome, which treated death, renal-replacement therapy, and a doubling of creatinine level as equivalent components, is not a patient-centered outcome. “What clinicians need to consider is whether the results of an open-label trial conducted in a single, major U.S. medical center can be generalized to the ways in which their own patients survive, feel, and function,” the editorial said, noting that questions still remain regarding the safety and efficacy of available resuscitation fluids. The studies and the editorial were published by the New England Journal of Medicine on Feb. 27 and appeared in the March 1 issue.

Small hospitals may need intensive antibiotic stewardship programs to see meaningful results

Small hospitals may require intensive strategies to effectively reduce antibiotic use, a cluster randomized trial found.

Researchers randomized 15 small hospitals (range, 14 to 146 beds), none of which had antibiotic stewardship programs or routine infectious diseases consultation available, to implement one of three programs that varied in intensity. Program 1 provided basic education and tools, access to an infectious diseases hotline, and data on the utilization of antibiotics. In Program 2, hospitals received the same interventions, plus advanced education, audit and feedback from pharmacists for certain antibiotics, and locally controlled antibiotic restrictions. The most intensive intervention, Program 3, added audit and feedback on the majority of antibiotic prescriptions from pharmacists and involvement of a clinician trained in infectious diseases to approve restricted antibiotics and review microbiology results.

Primary outcomes were each hospital's change in total and broad-spectrum antibiotic use from baseline (January to December 2013) through the intervention period (April 2014 through June 2015), as well as the difference between programs in the magnitude of change in antibiotic use. Results were published online on Feb. 23 by Clinical Infectious Diseases.

Compared to baseline, hospitals that followed Program 3 had an 11% reduction in total antibiotic use (risk ratio, 0.89; 95% CI, 0.80 to 0.99) and a 24% decrease in broad-spectrum antibiotic use (risk ratio, 0.76; 95% CI, 0.63 to 0.91). In contrast, hospitals that followed Programs 1 and 2 saw no changes in antibiotic use. Differences in the magnitude of effect between programs were not statistically significant, although there was a trend favoring Program 3.

The study authors noted limitations, such as how investigators and hospital staff were not blinded to program assignment and that changes in antibiotic use in the implementation period, which included site training, were not captured in the analysis of the formal intervention. They added that the small number of hospitals within each program and heterogeneity between sites limited the study's power to detect a difference in the effect size between the programs.

The authors noted that since Jan. 1, 2017, The Joint Commission has required all hospitals to have an antibiotic stewardship program. “How small hospitals will meet these regulatory requirements is unclear . . . . [I]mplementing [antibiotic stewardship programs] in small hospitals was feasible and had an impact on antibiotic prescribing when central resources and [infectious diseases] expertise were utilized and local pharmacists were actively involved,” they wrote.

Aspirin, rivaroxaban similarly effective at preventing VTE after total hip or total knee arthroplasty

Aspirin and rivaroxaban worked similarly well at preventing symptomatic venous thromboembolism (VTE) after total hip or total knee arthroplasty in patients who had received a short postoperative course of rivaroxaban, a double-blind randomized controlled trial found.

The EPCAT II (Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty II) trial enrolled 3,424 patients (mean age, 62.8 years; 47.8% male) at 15 university-affiliated health centers in Canada (1,804 had total hip arthroplasty, and 1,620 had total knee arthroplasty). All patients received an initial five-day course of oral rivaroxaban (10 mg/d) after the procedure. Then, 1,707 patients were randomized to receive aspirin (81 mg/d), and 1,717 patients were randomized to continue their daily dose of rivaroxaban. At the time of randomization, a subgroup of 855 patients was already taking long-term aspirin of less than 100 mg/day (372 in the hip group and 483 in the knee group). These patients continued taking open-label aspirin as prescribed by their physician in addition to the assigned trial regimen.

Overall, the average length of stay after surgery was 3.5 days, and each prophylaxis strategy continued for nine days after knee arthroplasty and for 30 days after hip arthroplasty. The primary effectiveness outcome was symptomatic VTE (proximal deep venous thrombosis and pulmonary embolism), and the primary safety outcome was major or clinically relevant nonmajor bleeding. Results of the trial, which had no industry funding or support, were published Feb. 22 by the New England Journal of Medicine.

At 90 days, symptomatic VTE rates were similar in the aspirin group and the rivaroxaban group (11 [0.64%] patients and 12 [0.70%] patients, respectively; difference, 0.06 percentage point; 95% CI, −0.55 to 0.66 percentage point; P<0.001 for noninferiority and P=0.84 for superiority). Both groups had similar rates of major bleeding: eight (0.47%) patients in the aspirin group and five (0.29%) patients in the rivaroxaban group (difference, 0.18 percentage point; 95% CI, −0.65 to 0.29 percentage point; P=0.42). A combination of major bleeding and clinically relevant nonmajor bleeding was also similar between groups: 22 (1.29%) patients in the aspirin group and 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage point; 95% CI, −1.07 to 0.47 percentage point; P=0.43). All bleeding events consisted of overt hemorrhage at the surgical site.

The study authors noted limitations of the trial, such as how the entire cohort was not treated with a standardized protocol, which prevented the calculation of absolute rates of the primary outcomes for each prophylaxis strategy. In addition, relatively few very high-risk populations, such as patients with previous VTE, morbid obesity, and cancer, underwent randomization, so it is unknown how well each strategy would work in these groups, an accompanying editorial noted.

Nonetheless, “This large, randomized, double-blind trial is likely to be practice-changing, because the point estimates for the relative safety and efficacy of the two treatments are precise and the included patients represent a typical population undergoing joint-replacement surgery,” the editorialist wrote.

Ethics consults associated with positive user experiences, shorter length of stay in ICU

Clinical ethics consultations in the ICU are associated with helpful, though stressful, experiences and greater consensus among surrogates and clinicians, as well as shorter ICU length of stay, a systematic review and meta-analysis found.

Researchers reviewed 16 studies, published from 1988 to 2015, that assessed outcomes after clinical ethics consultations took place in the ICU. Eight of the included studies were retrospective cohort studies and had low risk of bias, and seven studies were randomized controlled trials or prospective controlled cohorts, none of which had low risk of bias (largely because none blinded participants). Twelve (80%) of the studies were conducted in the U.S. Settings included medical, surgical, medical-surgical, trauma, oncologic, and cardiothoracic surgery ICUs.

Primary outcomes were user satisfaction or experience, resolution of conflict, and ability to make a clinical decision. Resource utilization (e.g., ICU length of stay) was a secondary outcome. Results were published online on Feb. 1 by Critical Care Medicine and appeared in the May issue.

Ethics consultations in the ICU were associated with a positive user experience (106 of 116 surrogates/patients and 283 of 319 clinicians found them helpful), although 113 of 431 family members and clinicians found them stressful. Among 194 clinical decision-making events in three studies, consensus was more frequently achieved with a consultation than without (odds ratio, 4.09; 95% CI, 1.01 to 16.55; P=0.05). In addition, ethics consultation was associated with lower resource utilization, including significantly decreased length of stay in the ICU for both surviving and nonsurviving patients (mean difference, −7.13 days; 95% CI, −11.24 to −3.03 days; P=0.007).

The authors noted limitations of their review, such as a limited sample, a lack of generalizability to non-ICU populations, and heterogeneity between studies. They added that the outcomes measured in the studies are limited and that future studies should use more specific process measures (e.g., a “Quality of Communication Index”) to assess the quality of ethics consultations.