Nutrition, contrast and AKI, and more

Research summaries from ACP Hospitalist Weekly.

Nutritional support didn't reduce mortality in inpatients with high C-reactive protein levels

The effect of inpatient nutritional support appeared to vary by baseline inflammation status in a recent analysis.

Researchers conducted a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT). EFFORT included patients at risk for malnutrition (defined as a Nutritional Risk Screening 2002 score ≥3 points) admitted to medical wards of eight hospitals in Switzerland with an expected hospital stay of at least five days.

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Image by Getty Images

The hospitalized patients were randomized to receive either protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). This analysis included patients whose C-reactive protein (CRP) levels were measured at admission. Results were published by JAMA Network Open on March 10.

Of the 1,950 patients in the analysis (median age, 75 years; interquartile range, 65 to 83 years), 27.3% had low levels of inflammation (CRP level <10 mg/L), 45.9% had moderate levels of inflammation (10 to 100 mg/L), and 26.8% had high levels of inflammation (>100 mg/L). Overall, compared with the control group, patients receiving nutritional support showed a significant reduction in 30-day mortality (adjusted odds ratio, 0.61; 95%, CI, 0.43 to 0.86; P=0.005). However, in the subgroup of patients with high inflammation, nutritional support was not associated with a reduction in mortality (adjusted odds ratio, 1.32; 95% CI, 0.70 to 2.50; P=0.390). The authors found that inflammation had a significant modifying association on the effect of nutritional support (P=0.005 for interaction) and that this was similar in the subgroup of patients with infection, suggesting that inflammation rather than infection was the main driver of the results.

The results could help explain the heterogeneity of results in previous trials of nutritional support, particularly the lack of benefit seen in trials among critical care patients, the study authors said. This study, which was conducted in lower-risk ward patients, demonstrates that “patients do benefit from nutritional support, but those with initially very high levels of CRP and thus marked inflammation may not respond,” the authors said.

They cautioned that the results do need to be validated in an independent sample, since they were drawn from a secondary analysis. Other limitations include small sample size, lack of information about cytokines other than CRP, and possible confounding.

Angiography with contrast associated with AKI, but clinically significant cases rare

While contrast-associated acute kidney injury (CA-AKI) is associated with an increased relative risk of serious adverse outcomes at 90 days, incidence of clinically significant cases appears low, a study found.

Researchers sought to characterize the relative risk for and incidence of serious adverse outcomes following CA-AKI and determine any association between preangiography estimated glomerular filtration rate (eGFR) and adverse outcomes. Results were derived from data in the Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial. All patients in PRESERVE had a preangiography eGFR of 15 to 44.9 mL/min/1.73 m2 or a preangiography eGFR of 45 to 59.9 mL/min/1.73 m2 and diabetes mellitus. The primary outcome of the current study was death, need for dialysis, and/or persistent kidney dysfunction at 90 days. Results were published March 16 by the Journal of the American College of Cardiology.

An association was found between CA-AKI and the primary outcome (odds ratio [OR], 3.93; 95% CI, 2.82 to 5.49; P<0.0001), which persisted after adjustment for patients' age, sex, urine albumin-to-creatinine ratio, diabetes, and myocardial infarction (odds ratio, 3.98; 95% CI, 2.81 to 5.63; P<0.0001). Among the overall study cohort, 1.2% (53 of 4,418 patients) developed clinically significant CA-AKI. Compared with the 138 patients who developed the primary outcome without CA-AKI, the 53 patients who developed the primary outcome after CA-AKI were more likely to have diabetes, to have received iso-osmolal iodixanol and a higher volume of contrast, and to have undergone angiography via the femoral artery.

The researchers concluded that in patients with chronic kidney disease and complete preangiography data on serum creatinine level, exposure, and outcomes, the development of CA-AKI following angiography was associated with an increased relative risk for serious adverse outcomes at 90 days but that the incidence was very low. It is not clear from their study whether CA-AKI causes serious adverse outcomes or is a marker of patients at higher risk, they said. “These observations will inform risk/benefit assessments for angiographic procedures, enhance the use of clinically indicated angiography in patients with [chronic kidney disease], and influence the design of future clinical trials on interventions for the prevention of AKI,” the authors wrote.

An accompanying editorial noted that the role of contrast in causing renal injury and adverse consequences for patients remains unclear, that the insensitivity of serum creatinine to identify changes in kidney function may contribute to this lack of clarity, that the incidence of CA-AKI in patients treated with contemporary hydration regimens is low, and that the incidence of combined AKI and sustained kidney injury is even lower. “Nevertheless, we are not yet ready to conclude that CA-AKI is truly an innocent bystander: the concern for AKI in the cardiology community should continue. Identification of patients at risk, appropriate fluid administration, and minimization of contrast dose remain important for now,” the editorialists wrote.

Empiric antibiotics for pneumonia often not de-escalated after negative cultures

Fewer than 15% of eligible patients with pneumonia had empiric antibiotic coverage de-escalated immediately following negative cultures for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas in a recent study.

The retrospective cohort study included 14,710 adults hospitalized with pneumonia from July 2010 to June 2015 at 164 U.S. hospitals participating in the Premier Healthcare Database. All patients had negative blood and/or respiratory cultures and had received an empirical anti-MRSA drug together with at least one antipseudomonal drug other than a quinolone by hospital day 1. Antibiotic de-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Researchers assessed the association between de-escalation on hospital day 4 and subsequent all-cause in-hospital mortality, transfer to an ICU, receipt of invasive mechanical ventilation or vasopressors, antibiotic re-escalation, and Clostridioides difficile infection. They also measured length of stay and cost. Results were published online on March 4 by Clinical Infectious Diseases.

By hospital day 4, 77 patients died, 12,786 patients were on either medication, and 1,924 (13%) had both initial empiric drugs stopped. Hospitals' de-escalation rates ranged from 2% to 35%, with a median of 13%. Overall de-escalation rates were less than 50% even among patients at lowest risk for mortality at hospitals in the top quartile of de-escalation. De-escalation was more common in hospitals with more than 401 beds compared to hospitals with less than 200 beds (9.7% vs. 5.9%), in teaching institutions compared to others (9.7% vs. 6.3%), and in urban compared to rural hospitals (8.2% vs. 6.9%).

At the patient level, de-escalation was significantly associated with reductions in most negative outcomes studied. In propensity-adjusted analyses, patients whose antibiotics were de-escalated had lower odds of subsequent transfer to the ICU (adjusted odds ratio [OR], 0.38; 95% CI, 0.18 to 0.79), late invasive mechanical ventilation (adjusted OR, 0.25; 95% CI, 0.09 to 0.66), and late vasopressor use (adjusted OR, 0.13; 95% CI, 0.04 to 0.44), as well as shorter length of stay (risk-adjusted ratio of means, 0.76; 95% CI, 0.75 to 0.78) and lower hospitalization costs (risk-adjusted ratio of means, 0.74; 95% CI, 0.72 to 0.76). De-escalation was not significantly associated with 14-day mortality (adjusted OR, 0.65; 95% CI, 0.39 to 1.08) or with developing C. difficile infection (adjusted OR, 1.33; 95% CI, 0.40 to 4.47). Only 13 patients (1.4%) were re-escalated to broad-spectrum antibiotics during hospitalization.

The study authors noted limitations, such as the use of ICD-9 codes to define the study cohort, the inability to measure clinical severity, and the potential for residual unmeasured confounders. They emphasized that recent pneumonia guidelines recommend de-escalation of empiric therapy against MRSA and Pseudomonas following negative cultures. “These data suggest that physicians will need to substantially change their response to negative cultures for most non-critically ill patients if they are to adhere to the new guidelines,” they concluded.

Low SBP during acute MI admission may predict 1-year mortality in elderly patients

Elderly patients who have low systolic blood pressure (SBP) in the 48 hours after admission for acute myocardial infarction (MI) may be at higher risk for death in the next year, according to a recent study.

Researchers in France performed a prospective observational study to identify optimal SBP soon after admission for acute MI and to determine its prognostic value for cardiovascular death in elderly patients. Patients older than age 75 years who were admitted to a coronary care unit for acute MI from 2012 to 2015 and were discharged alive were included in the study. Those who died in the hospital, those who had cardiogenic shock, and those with end-stage renal disease were excluded. Average SBP was calculated from at least three values recorded during the first 48 hours after admission, and patients were divided into those with an average SBP below 125 mm Hg and those with an average SBP of at least 125 mm Hg. Events at one year were determined by mailing or telephone interview with patients, family members, or general practitioners. The primary outcome was one-year cardiovascular mortality. The study results were published Feb. 26 by the Journal of the American Heart Association.

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Image by Getty Images

The study included 814 patients, 391 (48%) with an average SBP below 125 mm Hg. Median age of the study sample was 82 years, and 51% of patients were women. Patients who died of a cardiovascular cause during one-year follow-up were more likely to have cardiovascular risk factors (e.g., age and diabetes) or low body mass index and had higher scores on the Global Registry of Acute Coronary Events. Patients with low average SBP after admission had a higher risk for cardiovascular death at one year than those with an average SBP of at least 125 mm Hg (12.0% vs. 6.6%; P=0.008) and also had higher rates of all-cause death (19.2% vs. 12.8%; P=0.012). Low average SBP after admission was a strong and independent predictor of cardiovascular death at one year in a multivariable logistic regression analysis adjusted for several covariates (odds ratio, 1.91; 95% CI, 1.07 to 3.41).

The researchers noted that their study was missing some data, did not assess confusion, functional decline, or cognition, and could have been affected by confounding, among other limitations. They concluded that low average SBP during hospitalization for acute MI is a predictor of cardiovascular death at one year among elderly patients and that their results suggest a benefit of maintaining an average SBP above 125 mm Hg in the first 48 hours after an MI. “If confirmed, these findings could help to identify high-risk patients,” the authors wrote. They suggested that based on their results, hypotensive therapies should be considered with caution for short-term management of acute MI in this patient population.

Adjunctive strategies underused in moderate to severe ARDS, international study finds

Adjunctive strategies are commonly underused in the treatment of acute respiratory distress syndrome (ARDS), a recent study found.

Researchers used data from Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE), a prospective cohort study conducted in 2014 in 459 ICUs from 50 countries. The current analysis included 1,151 invasively ventilated patients with moderate to severe ARDS (defined as arterial oxygen partial pressure to fractional inspired oxygen ratio <150). Results were published by CHEST on Feb. 20 and appeared in the June 1 issue.

At 48 hours after ARDS onset, most of the patients (71%) had received neither widely available adjunctive strategies (neuromuscular blockade, prone positioning) nor those requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency oscillatory ventilation). The rate was similar (67%) in the subgroup of patients who did not survive ARDS. Of the 335 patients (29%) who did receive adjunctive strategies, 249 (74%) received a single strategy, and 86 (26%) received more than one. Although widely available adjunctive strategies were more commonly used than the specialized ones (70% vs. 30%), 63% of the patients receiving specialized adjunctive therapies did not receive prone positioning or neuromuscular blockade.

Factors associated with patients' receipt of adjunctive strategies included recognized ARDS, younger age, higher severity of illness, pneumonia, and difficult ventilation. There was also greater use of the adjunctive strategies in high-income European countries than in other places, which researchers speculated might be because the evidence for neuromuscular blockade and prone positioning was developed in these countries.

Overall, the study results show underuse of adjunctive strategies in moderate to severe ARDS “which is of significant concern,” the study authors said. “There was no clear pattern in regard to the use of adjuncts in terms of their supporting evidence base or their resource requirements,” they wrote. The underuse and absence of a sequential approach, which would implement the widely available strategies before the specialized ones, support previous proposals for protocols to guide use according to hypoxemia, the authors said. “A more consistent and evidence driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate-severe ARDS,” they concluded.

Limitations of the study include that the findings were observational and so causality cannot be inferred and that data were gathered in 2014 and practice may have changed since, the authors said. In addition, no data were available on the sequence in which adjunctive strategies were used in patients who received more than one.

No sedation, light sedation associated with similar outcomes in ventilated ICU patients

For mechanically ventilated ICU patients, no sedation and light sedation were associated with similar outcomes, a recent trial found.

The European multicenter trial randomized 710 mechanically ventilated ICU patients to a plan of either no sedation or light sedation (defined as a score of −2 to −3 on the Richmond Agitation and Sedation Scale [RASS]) with daily interruption. Seven hundred of the patients were included in the intention-to-treat analysis. Results were published by the New England Journal of Medicine on Feb. 16 and appeared in the March 19 issue.

The groups were similar at baseline, except that the nonsedation group had a one-point higher Acute Physiology and Chronic Health Evaluation II score at baseline. The mean RASS score increased from day 1 to day 7 in both groups (nonsedation: −1.3 to −0.8; sedation: −2.3 to −1.8). There was no significant difference in 90-day mortality (42.4% in the nonsedation group vs. 37.0% in the sedated group; difference, 5.4 percentage points; 95% CI, −2.2 to 12.2; P=0.65).

Secondary outcomes were major thromboembolic events, days free from coma or delirium, acute kidney injury according to severity, and ICU-free and ventilator-free days. There was a major thromboembolic event in only one patient (0.3%) in the nonsedation group and 10 patients (2.8%) in the sedation group. All other secondary outcomes did not differ significantly between the trial groups, but these results could not be adjusted for multiple comparisons, so no formal inferences could be made from them, the authors said. They noted that the observed lack of effect on outcomes might have been due to less difference in depth of sedation between the study groups than was intended.

An accompanying editorial noted that 27% of the patients in the nonsedation group received sedation in the 24 hours following randomization. The editorial identified a number of other limitations to the study: Patients were excluded if their ratio of partial pressure of arterial oxygen (in mm Hg) to fraction of inspired oxygen was 68 or less, 14.6% of eligible patients declined to participate, and the actual difference between groups in the time with coma or delirium could have been anywhere between 1 and 24 hours.

“The results from this trial are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically with the aim of discontinuing it as early as possible or at least interrupting it daily. Such monitoring should be performed continuously (24 hours per day, every day) on the basis of standardized criteria that can be applied uniformly in an ICU,” the editorial said.