Anemia, antibiotic overuse, and more

Research summaries from ACP Hospitalist Weekly.

Anemia common after hospitalization for critical illness

Patients hospitalized for critical illness often have postdischarge anemia that may persist for up to a year, according to recent findings.

Researchers performed a population-based cohort study in one county in Minnesota to look at changes in anemia status during and after critical illness, as well as the associations between hemoglobin levels and mortality postdischarge. Main outcome measures were hemoglobin levels in the 12 months before hospitalization, during hospitalization, and in the 12 months postdischarge. Anemia was categorized as mild (hemoglobin level, 10.0 to <12.0 g/dL in women or 10.0 to <13.5 g/dL in men), moderate (hemoglobin level, 8.0 to <10.0 g/dL), or severe (hemoglobin level, <8.0 g/dL). Other outcomes measured included complete recovery from anemia, defined as nonanemic status by 12 months after hospitalization, and 12-month mortality rates. The results were published Sept. 24, 2020, by JAMA Network Open.

The study was conducted from Jan. 1, 2010, to December 31, 2016, and data analysis was performed from June 1 to Dec. 30, 2019. A total of 6,901 adults admitted to intensive care were included; of these, 3,792 (55%) were men, and the median age was 67 years. Among the 83% of patients who had prehospitalization hemoglobin levels available, the median level was 13.1 g/dL (interquartile range [IQR], 11.6 to 14.4 g/dL), and 41% had anemia. At hospital discharge, the median hemoglobin level was 10.8 g/dL (IQR, 9.5 to 12.4 g/dL), and 80% of patients had anemia (58% mild, 39% moderate, and 3% severe). Posthospitalization anemia prevalence was 56% (95% CI, 55% to 58%) at three months, 52% (95% CI, 50% to 54%) at six months, and 45% (95% CI, 43% to 47%) at 12 months in patients who were living and had hemoglobin measurements available.

Complete recovery from anemia at 12 months was seen in 58% (95% CI, 56% to 61%) of those with mild anemia at discharge, 39% (95% CI, 36% to 42%) of those with moderate anemia, and 24% (95% CI, 15% to 34%) of those with severe anemia. Among patients without anemia at baseline who survived hospitalization, 74% were anemic at discharge; rates of complete recovery in this group at 12 months were 73% (95% CI, 69% to 76%) for mild anemia, 62% (95% CI, 57% to 68%) for moderate anemia, and 59% (95% CI, 35% to 82%) for severe anemia. After multivariable adjustment, higher hemoglobin levels at discharge were associated with decreased mortality (hazard ratio, 0.95 per 1-g/dL increase; 95% CI, 0.90 to 0.99; P=0.02).

The authors noted that they had no data on causes of anemia, that hemoglobin levels were not uniformly available after discharge, and that their results may not be generalizable to other critically ill populations, since their study included mostly White patients from one geographic location. They concluded that anemia appears common after critical illness and often persists in the year after hospital discharge. “Further studies are necessary to more fully evaluate associations between posthospitalization anemia and patient-important clinical outcomes,” the authors wrote. “In addition, studies are warranted to distinguish patients likely to recover from anemia after hospitalization from those who may experience prolonged anemia; the latter group may benefit from close outpatient follow-up and/or targeted anemia management strategies.”

Nearly half of inpatients with pneumonia or urinary tract infection were overprescribed antibiotics after discharge

Nearly half of hospitalized patients treated for pneumonia or urinary tract infection (UTI) had antibiotic overuse after discharge, although overuse varied widely across hospitals, a recent study found.

Researchers looked at a cohort of non-critically ill hospitalized patients who received antibiotic therapy for pneumonia or UTI between July 1, 2017, and July 30, 2019, at 46 Michigan hospitals participating in the Michigan Hospital Medicine Safety Consortium, which has collected data on patients treated for these infections. The primary outcome was the percentage of patients discharged with antibiotic overuse, defined as unnecessary antibiotic use, excess antibiotic duration, or suboptimal fluoroquinolone use. When evidence for appropriate treatment was conflicting, treatment was considered appropriate. Results were published online on Sept. 11, 2020, by Clinical Infectious Diseases.

Image by Getty Images
Image by Getty Images

Of 21,825 patients treated for infection (n=12,445 pneumonia; n=9,380 UTI), 15,803 (72.4%) were prescribed an antibiotic at discharge, most commonly a fluoroquinolone (34.2%). Overall, 10,709 (49.1%) patients had antibiotic overuse after discharge (56.9% pneumonia; 38.7% UTI). The mean duration of antibiotic overuse after discharge was four days (interquartile range, 2 to 6). In patients treated for pneumonia, 63.1% of overuse days after discharge were due to excess antibiotic duration (19.5% suboptimal use of fluoroquinolones; 17.4% unnecessary therapy). In patients treated for UTI, 43.9% of antibiotic overuse days were due to unnecessary treatment of asymptomatic bacteriuria (37.3% excessive therapy; 18.7% suboptimal use of fluoroquinolones). Overall, the majority of fluoroquinolone overuse after discharge was due to a combination of unnecessary and excessive therapy rather than suboptimal use of fluoroquinolones. The percentage of patients discharged with antibiotic overuse varied fivefold among hospitals, from 15.9% (95% CI, 8.7% to 24.6%) to 80.6% (95% CI, 69.4% to 88.1%).

Limitations of the study include its observational design and the difficulty of defining and quantifying antibiotic overuse, the authors noted. They added that the results likely underestimated overuse because they focused on fluoroquinolones rather than including all potential types of suboptimal antibiotic therapy (e.g., prescribing broad-spectrum antibiotics when narrow therapy would suffice).

“Given the ubiquity of overuse after discharge it is imperative that stewardship programs enact interventions to improve prescribing—which often means stopping antibiotics—at care transitions. . . . Currently, however, discharge prescriptions are difficult for hospitals to monitor as they are often filled by external pharmacies and are not easy to count electronically,” they wrote.

Biomarkers as accurate as troponin plus clinical signs for identifying type 2 MI

Several biomarkers that could be used to discriminate type 2 myocardial infarction (MI) from type 1 were identified by a recent study.

This post hoc analysis of the multicenter, international CHOPIN study included 2,071 patients who had presented to an ED with chest pain. Two cardiologists adjudicated whether the patients had type 1 (n=94) or type 2 MI (n=176). The researchers then analyzed the ability of several biomarkers alone or in combination to discriminate between the conditions, using the area under the receiver-operating curve, as well as to predict all-cause mortality and major cardiovascular events within 180 days. Results were published by Circulation on Aug. 21, 2020, and appeared in the Oct. 20, 2020, issue.

Patients with type 1 MI had higher baseline levels of cardiac troponin I, while those with type 2 had higher levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET1), mid-regional pro-adrenomedullin (MR-proADM), and procalcitonin. The area under the ROC curve for the diagnosis of type 2 MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for troponin I (0.631). A combination of biomarkers (those listed above plus copeptin) had similar accuracy to a model that used nine clinical variables and troponin (0.854 vs. 0.884, P=0.294). In both type 1 and type 2 patients, troponin was not associated with mortality or major adverse cardiovascular events during follow-up, but the other biomarkers were.

“Our study adds to the literature by providing novel insights for several . . . biomarkers that can evaluate different pathophysiologic processes involved in [type 2 MI],” the authors said. They noted that the higher levels of MR-proANP, CT-proET1, and MR-proADM seen in the type 2 MI patients are reflective of volume overload and congestion. Limitations of the study include that it used older troponin assays than are available now and that the numbers of study patients and clinical events were small. The authors called for additional research to confirm the findings.

“At this time, it is recommended to make use of detailed history, physical examination and standard laboratory testing for the diagnosis of [type 2 MI]. However, the weaknesses in this approach should also be recognized because these clinical findings can be more subjective and are at risk for disagreement in interpenetration by different physicians whereas biomarkers are more objective,” they wrote.

Complex in-hospital treatment linked to worse outcomes for heart failure

Intensification of heart failure therapy beyond IV diuretic treatment during an admission was associated with a longer hospital stay and higher mortality risk, according to a recent study.

Researchers used electronic health record data from 2007 to 2018 to examine in-hospital treatment patterns and associated outcomes among U.S. patients with heart failure with reduced ejection fraction. Patients were included if they had a primary diagnosis of heart failure with an ejection fraction of 40% or less, were hemodynamically stable at hospital admission, did not have acute coronary syndrome or end-stage renal disease, and were treated with IV diuretics within 48 hours of admission. They were categorized into four groups by treatment complexity: intensified (initiation of mechanical support, inotropes, or IV vasodilators on hospital day 2 or later), IV diuretic reinitiation (diuretics initiated after at least a one-day gap without intensified treatment), IV diuretic dose increase and/or combination diuretic treatment (increased IV diuretic dose or administration of at least two different diuretics on the same day, at least one via IV), and uncomplicated (none of the above). The results of the study were published Aug. 12, 2020, by JACC: Heart Failure and appeared in the Nov. 8, 2020, issue.

Overall, 22,677 patients hospitalized for heart failure with reduced ejection fraction were included in the study. Median age was 72 years, and 36% were women. Among all patients, 14,868 (65.6%) had uncomplicated hospitalizations, and treatment did not escalate beyond initial IV diuretic therapy. For the remaining 7,809 patients (34.4%), 1,983 (25.4%) received IV diuretic dose increase/combination diuretic treatment as their highest level of therapy, 2,814 (36%) received IV diuretic reinitiation, and 3,012 (38.6%) had intensified therapy. Among all patients, 19% had IV diuretic agents reinitiated, and in 26% of these patients, IV diuretics were reinstated multiple times. Twelve percent of all patients received simultaneous treatment with multiple diuretics, and 61% were switched to oral diuretics before hospital discharge. When compared with uncomplicated treatment, IV diuretic reinitiation and intensified treatment were associated with a significantly longer median length of stay (four days, eight days, and 10 days, respectively) and higher mortality rates in-hospital (1.6%, 4.2%, and 13.2%) and 30 days postdischarge (5.2%, 9.7%, and 12.7%).

The authors noted that their data were observational, that causal relationships could not be determined, and that the reasons for clinicians' treatment decisions were not available, among other limitations. They concluded that in this study involving data from real-world U.S. clinical practice, one-third of patients hospitalized for heart failure with reduced ejection fraction experienced treatment escalation beyond initial IV diuretics and that treatment for these patients varied widely. In addition, patients who received complex treatment, such as reinitiation of IV diuretics, IV diuretic dose increase, and combination diuretics, were more likely to have longer hospital stays and higher in-hospital and postdischarge mortality rates.

“These findings support major inefficiencies and uncertainties regarding the in-hospital treatment of HFrEF [heart failure with reduced ejection fraction] in U.S. practice and highlight potential adverse consequences for health resource use and patient outcomes,” the authors wrote. “Further efforts are needed to develop standardized and evidence-based approaches to in-hospital HFrEF care.”