Therapeutic hypothermia, HAI network, and more

Summaries from ACP Hospitalist Weekly.

Moderate hypothermia improved neurologic outcomes after cardiac arrest with nonshockable rhythm

Patients who underwent moderate therapeutic hypothermia after resuscitation from cardiac arrest with nonshockable rhythm were more likely to have a favorable neurologic outcome, a recent trial found.

The trial included 584 patients with coma who had been admitted to 25 French ICUs after resuscitation from cardiac arrest with nonshockable rhythm (asystole or pulseless electrical activity) from January 2014 through January 2018. They were randomized to either moderate therapeutic hypothermia (33 °C during the first 24 hours) or targeted normothermia (37 °C). The primary outcome was survival with a favorable neurologic outcome at 90 days, defined as a 1 or 2 on the Cerebral Performance Category (CPC) scale. Results were published by the New England Journal of Medicine on Oct. 2, 2019, and appeared in the Dec. 12, 2019, issue.

Image by Getty Images
Image by Getty Images

Three patients (all in the hypothermia group) withdrew consent, so 581 were included in the analysis. On day 90, 29 of 284 patients (10.2%) in the hypothermia group and 17 of 297 (5.7%) in the normothermia group met the primary outcome (difference, 4.5 percentage points; 95% CI, 0.1 to 8.9; P=0.04). Mortality at 90 days did not differ significantly between groups (81.3% and 83.2%, respectively; difference, −1.9 percentage points [95% CI, −8.0 to 4.3]), nor did incidence of prespecified adverse events.

The authors concluded that moderate therapeutic hypothermia led to a higher percentage of patients surviving with a favorable neurologic outcome, and they noted that previous research in this area has found mixed results. “Cardiac arrest is a highly heterogeneous entity, and many factors may affect the efficacy of hypothermia,” they wrote. They calculated that based on the study results the number needed to treat (NNT) with hypothermia to have one additional patient survive with a CPC of 1 or 2 would be 22, compared to NNTs to prevent one patient death of 15 for bystander CPR and 112 for epinephrine.

The study did have a number of limitations, including that a substantial proportion of patients had body temperatures above 38 °C and that the study used targeted temperature management for 56 to 64 hours in the hypothermia group and for 48 hours in the normothermia group. “Last, the fragility index value of 1 for our trial indicates that an outcome change in a single patient would make the difference in the primary outcome nonsignificant,” the authors said.

CDC's STRIVE initiative takes network approach to HAI reduction

The CDC's STRIVE (States Targeting Reduction in Infections Via Engagement) initiative used a network-driven approach to improving quality in the area of health care-associated infections (HAIs).

STRIVE was developed in partnership with the American Hospital Association's Health Research & Educational Trust and state, hospital, and academic entities to improve infection prevention and control practices in U.S. hospitals with a disproportionately high HAI burden. The overall objective of STRIVE was to identify, partner with, and collaborate with these hospitals by pairing national subject matter experts with state, regional, and local organizations. Four hundred sixty-two hospitals in 28 states and the District of Columbia were recruited, and 443 completed the program, which lasted 12 months.

The program's results were published as a supplement, which was supported by the Health Research & Educational Trust, on Oct. 1, 2019, by Annals of Internal Medicine.

STRIVE's educational and training components were implemented through webinars and Web-based infection prevention modules with site visits from national subject-matter experts; monthly coaching by state partners; and monthly learning action forums. Reductions in Clostridioides difficile infection, central line-associated bloodstream infection, catheter-associated urinary tract infection, and hospital-onset methicillin-resistant Staphylococcus aureus bloodstream infection were chosen as key targets of the STRIVE initiative. All hospitals in the program followed a structured, stepwise curriculum to reduce HAIs, emphasizing horizontal infection prevention strategies, such as hand hygiene and environmental cleaning, and socioadaptive solutions, such as team building and leadership engagement.

While some of the STRIVE hospitals saw improvements in outcome and process measures, and some were able to maintain or achieve infection rates of zero during the intervention period, no statistically significant change over time was seen from baseline for any of the targeted HAIs. Editorialists said this could be explained in part by limitations in data collection and analysis as well as inconsistent analysis. “Qualitative findings did show stronger stakeholder relationships had been established that could align and sustain HAI prevention across the entire patient continuum of care,” the editorialists wrote.

The editorialists called for additional efforts to standardize HAI prevention processes throughout the U.S. health care system. “This commitment includes educating health care workers in HAI prevention, robust processes to measure infection rates, and continuous use of evidence-based practices with every patient in every setting by all clinicians and team members,” they wrote.

The supplement includes 14 articles detailing the steps taken to reduce each targeted infection, the overarching structure of the initiative, and other related topics. All of the STRIVE papers are accessible on the Annals of Internal Medicine website.

Simplified lung ultrasonography quantifies pulmonary congestion in acute heart failure

A simplified lung ultrasonography method predicted adverse events, readmissions, and mortality among hospitalized patients with acute heart failure, a recent study found.

The prospective observational study was conducted at two sites, one in Boston and one in Glasgow. At both sites, a four-zone lung ultrasound was performed early during hospitalization for acute heart failure. At the Boston site, another ultrasound was done at discharge. B-lines were quantified off-line, blinded to clinical findings and outcomes, by a core laboratory. Results were published in the October 2019 JACC: Heart Failure.

A total of 349 patients (median age, 75 years; 59% men; mean ejection fraction, 39%) underwent the initial ultrasound, and they had B-line sums ranging from 0 to 18. The risk of an adverse in-hospital event increased with the number of B-lines: The odds ratio for each B-line tertile was 1.82 (95% CI, 1.14 to 2.88; P=0.011). In the 132 patients who got ultrasounds at discharge (a median of six days later), B-line count had decreased from a median of 6 to 4 (P<0.001). The risk of heart failure re-hospitalization or all-cause death was greater in patients with a higher number of B-lines at discharge, with the effect waning with time after discharge (unadjusted hazard ratios, 3.30 [95% CI, 1.52 to 7.17; P=0.002] at 60 days, 2.94 [95% CI, 1.46 to 5.93; P=0.003] at 90 days, and 2.01 [95% CI, 1.11 to 3.64; P=0.021] at 180 days. The association between number of B-lines and adverse outcomes persisted after adjustment, including for N-terminal pro B-type natriuretic peptide (NTproBNP) levels.

The results show that “most patients had a measurable number of B-lines on simplified 4-zone lung ultrasonography (LUS) after admission to the hospital, despite the absence of clinical or radiologic signs of congestion in many,” the study authors said. Previous research has used an 8- or 28-zone scanning method, and “a simplified LUS imaging protocol in the in-hospital setting is attractive due to its shorter performance time and lower likelihood of missing data,” they said. Lung ultrasound also offers the advantage of providing a spectrum of pulmonary congestion findings rather than the binary results of clinical examination or chest X-ray, the authors added.

However, they cautioned that lung ultrasound needs to be tested prospectively before it is put into practice as a triage tool for patients admitted with heart failure. The authors also suggested that randomized trials could look at using B-lines as a target for inpatient heart failure therapy. Limitations of the study included that patients at only one site received ultrasound at discharge and that ICU patients were excluded from the study.

An accompanying editorial comment credited the study for “bringing some clarity to the reliability of point-of-care LUS” but warned that “whether LUS adds clinically useful information beyond that of a careful history and physical examination is unknown.” Both the study and the editorial pointed to the failure of NTproBNP-guided therapy as a cautionary example. “In summary, much more work is needed to understand the appropriate incorporation of LUS into the routine care of patients with heart failure, but [these] findings do point the way forward,” the editorialists said.

Fluoroquinolones prescribed frequently, often inappropriately, at hospital discharge, study finds

Fluoroquinolones are often prescribed at hospital discharge, and many such prescriptions may not be appropriate, according to a recent study.

Researchers performed a retrospective cohort study of patients at 122 Veterans Health Administration (VHA) acute care hospitals during 2014 to 2016 to look at patterns of fluoroquinolone prescribing at discharge. Prescriptions were also compared among nine hospitals that responded to a VHA survey about antimicrobial stewardship and self-reported use of prospective audit and feedback, restrictive policies, or no strategies to optimize fluoroquinolone prescribing. For these hospitals, manual chart review was used to determine how often fluoroquinolones were prescribed appropriately. The study results were published Sept. 28, 2019, by Clinical Infectious Diseases.

The study included 1,685,475 admissions and 1,727,478 fluoroquinolone days of therapy. Of these, 674,918 (39.1%) were prescribed for inpatients and 1,052,560 (60.9%) were prescribed at discharge. The diagnoses most likely to be associated with postdischarge fluoroquinolone use were urinary tract infection (18.7%) and acute exacerbations of chronic obstructive pulmonary disease (14.5%). Overall, 39,587 postdischarge fluoroquinolone prescriptions (30.8%) were for patients who had not received a fluoroquinolone while hospitalized.

In the manual chart review, which involved 375 patients at the nine included hospitals, those that reported using restrictive policies had lower fluoroquinolone exposure postdischarge than those that reported no strategy (3.8% vs. 9.3%; P=0.012). No significant difference in fluoroquinolone exposure was seen in hospitals that used prospective audit and feedback versus those that used no strategy. Postdischarge fluoroquinolones were considered to be inappropriate on manual chart review in 154 of 375 patients (41.4%). Hospitals that reported no strategy to optimize fluoroquinolone use were more likely to have inappropriate use postdischarge than those that used restrictive policies or self-reported audit and feedback (52.8% vs. 35.2%; P=0.001).

The researchers noted that survey responses were self-reported, that differences in administration of stewardship strategies by hospital were not considered, and that there is no gold standard for the appropriateness of fluoroquinolone use, among other limitations. They concluded that in their study, most exposures to fluoroquinolones occurred after discharge and a large proportion of these prescriptions were inappropriate, especially at hospitals that did not currently have a strategy for managing fluoroquinolone prescribing in place. “Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone prescribing should also focus on antimicrobial-prescribing at hospital discharge,” the authors wrote.

An accompanying editorial called hospital discharge “a major temporal moment for [antimicrobial stewardship]” and noted that the current study, despite its limitations, offered several opportunities for improvement in this area. Most of the inappropriate fluoroquinolone use at discharge was related to excessive duration or to selection error, meaning that the drugs should not have been prescribed in the first place, the editorialist said.

“[Antimicrobial stewardship] opportunities at hospital discharge warrant further study to elucidate best practices and strategies as standard protocols and checklists have demonstrated in other general healthcare and [antimicrobial stewardship] settings,” the editorialist wrote. “Successful implementation of [antimicrobial stewardship] at this critical transition point will need to leverage and engage frontline providers, staff, pharmacists, case management, nurses and the entire care team to impact this unmet need, optimize antibiotic use, and improve patient care.”

White patients had better outcomes after targeted temperature management than nonwhite patients

White patients were more likely than nonwhite patients to have a good outcome after postcardiac arrest targeted temperature management, a recent study found.

Researchers retrospectively assessed racial and ethnic disparities in postcardiac arrest outcomes in 367 patients undergoing targeted temperature management, including continuous electroencephalogram monitoring. Participants (non-Hispanic white, n=247; Hispanic/nonwhite, n=120) were treated in ICUs at a single tertiary care hospital, and their outcomes were assessed as good (Cerebral Performance Category 1-2) versus poor (Cerebral Performance Category 3-5) at hospital discharge. Results were published online on Sept. 25, 2019, by Critical Care Medicine and appeared in the January issue.

White patients were more likely to have good outcomes than nonwhite patients (85 [34.4%] patients vs. 26 [21.7%] patients; P=0.015). In a multivariate model that included age, time to return of spontaneous circulation, cardiac rhythm at time of arrest, combined electroencephalogram/CT findings, Charlson Comorbidity Index, and insurance status, race/ethnicity was still independently associated with poor outcome (odds ratio, 3.32; P=0.003).

Comorbidities were lower in white patients but did not fully explain the difference in outcomes. Nonwhite patients were more likely to exhibit signs of early severe anoxic changes on CT or electroencephalogram, have higher creatinine levels, and receive dialysis but had longer duration to withdrawal of life-sustaining therapy. There was no significant difference in catheterizations or MRI scans. In a subgroup analysis of patients without early electroencephalogram or CT, white patients still had better outcomes than nonwhite patients.

The study authors noted that in most cases, race and ethnicity were self-reported and lacked objective verifications. They added that race and ethnicity were combined into a single parameter, particularly with respect to Hispanic patients, and that the study was not sufficiently powered to measure outcome differences between racial/ethnic groups.

The results suggest multiple reasons for poorer outcomes in nonwhite patients, including presentation with early severe anoxic injury and a greater number of comorbidities, the authors said. “Our findings suggest that improving rapid access to medical attention after cardiac arrest and optimizing baseline outpatient medical comorbidities may decrease the observed outcome disparities, but other, yet unmeasured factors likely contribute as well,” they concluded.

Electronic medication reconciliation not associated with better postdischarge outcomes

Use of electronic medication reconciliation during a hospital stay was associated with a decrease in medication discrepancies but did not seem to affect adverse drug events (ADEs) or other adverse outcomes, according to a Canadian study.

Researchers in Montreal performed a cluster randomized trial of patients discharged from two medical and two surgical units at McGill University Health Centre between October 2014 and November 2016. For patients in the intervention group, electronic medication reconciliation was used to retrieve information on community drugs from the provincial insurer and align it with information on drugs taken in the hospital. This could be done any time during the patient's stay to reconcile medications at admission, transfer, and discharge. In the control group, the community drug list was documented at admission by pharmacy staff for medical patients and by physicians and nurses for surgical patients, and the attending physician or resident used the list of current hospital medications to prescribe medications at discharge.

The study's primary outcome was ADEs in the 30 days postdischarge, while secondary outcomes included medication discrepancies, ED visits, readmissions, and a composite outcome of ED visits, readmission, and death up to 90 days postdischarge. ADEs were defined as injuries resulting from medical intervention related to a drug, including failure to restart a drug that was stopped or held during admission or an unintended duplication of therapy. Study results were published Sept. 20, 2019, by JAMA Network Open.

A total of 3,567 patients agreed to participate in the study. Of these, 2,060 (57.8%) were men, and the mean age was 69.8 years. During hospitalization, 76 patients died, leaving 3,491 patients who were included in the analysis (1,836 in the control group and 1,655 in the intervention group). The intervention and control groups did not differ significantly in risk for ADEs (4.6% vs. 4.0%; odds ratio [OR], 0.97; 95% CI, 0.33 to 1.48), ED visits (26.2% vs. 26.6%; OR, 0.83; 95% CI, 0.36 to 1.42), hospital readmissions (10.3% vs. 14.2%; OR, 0.22; 95% CI, 0.06 to 1.14), or the composite outcome (27.0% vs. 27.6%; OR, 0.75; 95% CI, 0.34 to 1.27) at 30 days. Patients in the intervention group did have significantly fewer medication discrepancies than those in the control group (26.4% vs. 56.0%; OR, 0.24; 95% CI, 0.12 to 0.57). ADEs were more likely to occur when changes were made to community medications (OR, 1.05; 95% CI, 1.01 to 1.10) and new medications (OR, 1.09; 95% CI, 1.01 to 1.18).

The authors noted that their study may not be generalizable since it was conducted at a single academic medical center and that unintentional medication discrepancies may have been overestimated in the control groups. They concluded that while electronic medication reconciliation reduced medication discrepancies among patients who were hospitalized, it did not appear to affect rates of ADEs or other outcomes. The authors noted that accreditation requirements for hospitals in Canada and the U.S. recommend medication reconciliation at admission, transfer, and discharge for all patients but that this standard has been difficult to meet due to resource requirements.

“Our results do not provide empirical support for hospital accreditation requirements that are based on the contention that medication reconciliation will reduce discrepancies that lead to ADEs, ED visits, hospital readmission, or death after discharge,” the authors wrote. “Our results do support the contention that interventions to reduce ADEs should be targeted to patients with high risk who have multiple changes made to their community medications and many new medications added to their therapeutic regimens.”

Primary care scheduling improved postdischarge follow-up

A scheduling assistance program to facilitate early postdischarge follow-up with a primary care physician improved follow-up rates but had less effect on readmissions, a study found.

Image by Getty Images
Image by Getty Images

Researchers at Beth Israel Deaconess Medical Center in Boston performed a retrospective cohort study to determine whether implementing a scheduling assistance program affected rates of primary care follow-up or readmissions after hospitalization. For adults discharged home after hospitalization, attending and resident physicians entered a discharge appointment request with an outpatient physician for a specified time period, and staff at the scheduling assistance program called the practice to make the appointment. The date and time of the appointment were chosen without patient input, and the details were automatically entered in the discharge instructions and discharge summary. Attending and resident physicians were able to request a new primary care physician for patients who did not have one or who wanted to change their existing physician.

The study's main outcome measures were rates of follow-up visits with a primary care physician within seven days of discharge and rates of hospital admission within 30 days of discharge. The researchers initially assessed differences in outcomes with and without the service, then performed an instrumental variable analysis using the interaction between the intervention and the day of the week of admission, since the scheduling service wasn't available on weekends. The study results were published online Sept. 18, 2019, by the Journal of Hospital Medicine.

From January 2011 to September 2015, the appointment service was used for 9,101 hospitalizations and was not used for 8,481. In multivariable analysis, the appointment service was associated with higher rates of primary care follow-up after discharge (difference, 31.9 percentage points; P<0.001) and decreased readmission rates (difference, −3.8 percentage points; P<0.001). In instrumental variable analysis, which used all hospitalizations before and after introduction of the intervention, from September 2008 to October 2015, the likelihood of a primary care follow-up visit was higher in those who used the discharge appointment service (estimated impact, 33.4 percentage points; P<0.01). However, no significant effect was seen on readmissions (estimated impact, −2.5 percentage points; P=0.80).

The researchers noted that their study involved only one academic medical center and general medicine and cardiology patients. In addition, they pointed out that they could not capture follow-up visits or hospitalizations that took place at other health systems, among other limitations. They concluded that use of a postdischarge appointment service substantially increased early follow-up with a primary care physician but had less clear benefit for preventing readmissions. Regardless of the latter finding, however, they noted that early primary care follow-up alone offers many advantages.

“We believe the dramatic increase observed in PCP [primary care physician] follow-up reflects the administrative complexity required for a patient to call their PCP's office and to schedule a follow-up appointment soon after they are discharged from the hospital,” the authors wrote. “Our study implies that simply requesting that a patient call their PCP to schedule a timely appointment is often impossible, and this may be particularly true for those who need to obtain a new PCP.”

Conservative oxygen strategy didn't reduce time on ventilator

Use of a conservative oxygen strategy for mechanically ventilated ICU patients did not reduce days on the ventilator or mortality, a recent study found.

The trial included 1,000 patients in Australia and New Zealand who were anticipated to require continued mechanical ventilation in the ICU. In both groups, the default lower limit for oxygen saturation as measured by pulse oximetry (SpO2) was 90%. In those randomized to conservative oxygen therapy, an alarm would sound if SpO2 went to 97%. In addition, their fraction of inspired oxygen (FiO2) was decreased to 0.21 if their SpO2 was at least 90%. In the control group, there were no specific measures limiting the FiO2 or the SpO2. Results were published by the New England Journal of Medicine on Oct. 14, 2019, and appeared in the March 7 issue.

There was no significant difference between groups in the study's primary outcome of ventilator-free days from randomization until day 28 (median of 21.3 days on conservative therapy vs. 22.1 days with usual care; absolute difference, −0.3 day [95% CI, −2.1 to 1.6 days]; P=0.80). The conservative group did spend more time with an FiO2 of 0.21 (median duration of 29 hours vs. 1 hour; absolute difference, 28 hours [95% CI, 22 to 34 hours]) and less time with an SpO2 exceeding 96% (27 hours vs. 49 hours; absolute difference, 22 hours [95% CI, 14 to 30 hours]). At 180 days, mortality was 35.7% in the conservative group and 34.5% in the usual care group (unadjusted odds ratio, 1.05; 95% CI, 0.81 to 1.37).

The findings differ from a previous single-center trial that found reductions in days on the ventilator and death with conservative oxygen use, the study authors noted. However, that study was smaller and included specific targets for SpO2 and FiO2 in the control group. A recent systematic review also found that a conservative strategy was associated with lower mortality, but again, many of the included trials used a more liberal strategy than the usual-care group in this trial and few critically ill patients were included.

Although overall this study found no improvement in the primary outcome, the results “are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic–ischemic encephalopathy,” the authors said, noting that this finding should be considered hypothesis-generating.

The study had a number of limitations, including the possibility of survival bias and less severe illness among eligible patients who were not enrolled in the trial compared to those who were. Differences in oxygen levels due to treatment assignment may also have affected clinicians' decisions about weaning and extubation, the authors noted.

More initial fluid didn't worsen outcomes in sepsis patients with heart, kidney, or liver disease

Guideline-directed fluid resuscitation was not associated with any increased risk in respiratory failure among patients with sepsis and heart failure, end-stage renal disease (ESRD), or cirrhosis, a study found.

The retrospective study included 208 patients with sepsis or septic shock and heart failure, ESRD, or cirrhosis who were treated in the medical ICU of a single hospital. Half had received the recommended IV crystalloid dosage of 30 mL/kg or more in the first six hours after sepsis diagnosis (standard group) and they were propensity score-matched with another 104 patients who had received less fluid (restricted group). Results were published by CHEST on Oct. 14, 2019, and appeared in the February issue.

There was no significant difference in the study's primary outcome of need for mechanical ventilation within 72 hours after initiation of fluid resuscitation (36 patients in the restricted group vs. 33 in the standard group; adjusted odds ratio, 0.74 [95% CI, 0.41 to 1.3]; P=0.34). Secondary outcomes of days alive and out of the ICU (P=0.64), ventilator days (P=0.96), and hours to intubation (P=0.55) were also similar. The authors concluded that intubation rates did not appear to differ by whether septic patients with cirrhosis, ESRD, or heart failure received guideline-recommended fluid resuscitation or were initially resuscitated with a lower fluid volume.

“The perception that patients with cirrhosis, ESRD or heart failure are vulnerable to volume overload has been a major barrier to weight-based fluid resuscitation,” the authors said, noting that recent studies have also found delayed fluid resuscitation in these patients. The evidence does show risks of receiving more fluid during an entire ICU stay, but this study and other research have not found harm associated with conducting initial resuscitation according to Surviving Sepsis Campaign recommendations, according to the authors. “It appears that positive fluid balance at later time points (and overall) is detrimental to respiratory status, however, there does not seem to be harm in achieving a resuscitation volume >30 mL/kg in the first 6 hours after sepsis diagnosis in this cohort,” they said.

However, the study is limited by its retrospective design and thus cannot establish causality. Patients in the restricted group had lower renal function and those in the standard resuscitation group were more likely to have a “do not intubate” code status, although the authors adjusted for these factors. “It was also difficult to determine why the patients in the restricted group did not receive the recommended volume of fluid resuscitation—whether it was their underlying co-morbidity that put them at risk of fluid overload or perhaps the patients clinically appeared to be less sick or had alternative plausible diagnoses,” the authors said.

They called for prospective studies of different fluid resuscitation approaches in these high-risk patients but they suggested that, in the meantime, “guideline based early fluid resuscitative efforts should not be omitted in patients with cirrhosis, [heart failure], and ESRD solely for concern of acute respiratory failure.”