Clinical Voices December 2021

Dec 01, 2021

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This month we feature coverage of the new sepsis guidelines, benefits of a medication combo for IHCA, reducing death rattle in end-of-life patients, and more. Plus, read the new President’s Column and a heartwarming Nurse Q&A.

Post-ICU Care: One Focus of New Sepsis Guidelines

Timely, coordinated resources and provider follow-up may help improve quality of life for these patients.

Protocols to determine pediatric death by neurologic criteria (DNC) vary widely in the U.S., particularly with apnea and ancillary testing, and better alignment with national guidelines could improve consistency and accuracy.

Updated guidelines for sepsis and septic shock call for changes in antimicrobial, hemodynamic and pulmonary management, as well as improving care after ICU discharge, including follow-up with patients to assess any new or long-term physical, cognitive or emotional problems.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021,” in Critical Care Medicine (CCM), the official publication of the Society of Critical Care Medicine (SCCM), aims to reflect best practices in sepsis screening and treatment for adults in hospital settings. The guidelines, which were last updated in 2016, also “represent greater geographic and gender diversity than previous versions.”

“Patients often have lengthy ICU stays and then face a long and complicated road to recovery,” notes an SCCM news release. “In addition to physical rehabilitation challenges, patients and their families often are uncertain how to coordinate care that promotes recovery and matches their goals of care.”

The guidelines recommend that a patient’s written and verbal discharge summaries include information about “ICU stay, sepsis and related diagnoses, treatments and common impairments after sepsis.” While not specifying a follow-up period, the guidelines note that “timely, coordinated resources and provider follow-up may lead to improved QoL [quality of life].”

In addition, AACN offers the on-demand webinar “Update Your Practice With the 2021 Sepsis Guidelines” during which presenter Maureen Seckel, an expert on sepsis who contributed to the guidelines, explains the changes.

Effect of IV High-Dose Vitamin C on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials,” a related article in CCM, finds that IV high-dose vitamin C administered to adults with sepsis does not significantly improve short-term mortality risk but does reduce duration of vasopressor use.

The meta-analysis — involving 11 randomized controlled trials and 1,737 patients — also reveals that vitamin C is associated with significantly greater declines in Sequential Organ Failure Assessment scores at 72 to 96 hours.

Medication Combo for IHCA Yields Benefits and Uncertainty

Study results indicate that long-term outcomes (benefit or harm) are not clear.

A combination of vasopressin and methylprednisolone for patients with in-hospital cardiac arrest (IHCA) can significantly improve the likelihood of return to spontaneous circulation compared with placebo, but long-term outcomes are uncertain.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial,” in JAMA: The Journal of the American Medical Association, involved 501 adults (mean age 71) treated at 10 hospitals in Denmark between October 2018 and January 2021.

“Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses.”

In the combination group, 42% of patients achieved return to spontaneous circulation compared with 33% in the placebo group — a statistically significant difference, the trial reports. At 30 days, 9.7% of patients in the combination group and 12% in the placebo were alive. In both groups, 7.6% of patients demonstrated favorable neurologic outcomes, and 90-day outcomes were similar. Data is still being collected on six-month and one-year outcomes.

In a related article in Physician’s Weekly, trial co-author Lars Andersen, Aarhus University Hospital in Denmark, notes that two smaller trials previously revealed promising results when combining vasopressin (a potent vasoconstrictor) and steroids (such as methylprednisolone) for patients with IHCA.

While beneficial effects reported in the current trial are not surprising, they are “disappointing” since there was “no effect on more long-term survival as seen in the earlier trials,” Andersen notes in the article. The results, he adds, are currently not enough to recommend use of the combination treatment.

Death Rattle Significantly Reduced in European Study

The scopolamine formulation used in the trial is not FDA approved in the U.S.

A randomized clinical trial testing the effectiveness of prophylactic measures for patients nearing the end of life resulted in less than half as many cases of death rattle.

Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life,” in JAMA: The Journal of the American Medical Association, notes that death rattle, which is “noisy breathing caused by the presence of mucus in the respiratory tract” is fairly common in patients who are dying. However, in this trial, prophylactic subcutaneous scopolamine butylbromide significantly reduced the rattle.

The double-blind trial was conducted at six hospice centers in the Netherlands from April 2017 to December 2019. “In this randomized clinical trial that included 162 patients [157 in primary analyses], a death rattle was observed at 2 consecutive time points 4 hours apart in 13% of patients in the scopolamine butylbromide group and in 27% of patients in the placebo group, a statistically significant difference,” the trial adds. Adverse effects — restlessness, dry mouth and urinary retention — occurred in a similar number of patients.

Despite the demonstrated benefits, “the results may have limited applicability to change current practice, particularly in the United States,” notes a editorial in JAMA. Although the effect of death rattle in nonverbal patients remains uncertain, the editorial acknowledges the likely benefit to family members who may find the sound distressing.

According to a related article in MedPage Today, the scopolamine formulation in the trial is not FDA approved in the United States, where only the as-yet-unstudied transdermal form is available. Other anticholinergic medications would also require comparison studies before practice recommendations could change, the article adds.

Many Patients Symptomatic Long-Term

A study reviews one-year outcomes for patients discharged after surviving COVID-19.

Adult patients hospitalized with COVID-19 had fewer persistent symptoms at 12 months than at six months, but half continue to have health problems, and mental health issues are a concern.

According to “1-Year Outcomes in Hospital Survivors With COVID-19: a Longitudinal Cohort Study,” in The Lancet, 88% of survivors returned to normal work and life within 12 months, and those with at least one persistent symptom decreased from 68% at six months to 49% at 12 months. However, dyspnea and anxiety or depression rose during the same time periods.

The follow-up study included 1,276 patients discharged from a hospital in Wuhan, China, between January and May 2020, of whom 7% had required high-flow oxygen or mechanical ventilation during hospitalization, and 4% were in intensive care. “Lung diffusion impairment and radiographic abnormalities” were common lingering symptoms for critically ill patients, the study notes, with 54% at the highest severity scale at 12 months.

Study limitations include tracking patients from the early stage of the pandemic, including a low proportion of critically ill patients, and about half of the initial patient group not completing necessary follow-ups to be included.

Additional resources include AACN blog posts “COVID-19: Persistent Symptoms, PICS, Post-Viral Syndrome or Something Else” and “My Journey With Long COVID.”

Other studies find that long-term COVID-19 symptoms are less common in children than in adults, with 98.4% of children fully recovered after eight weeks in one U.K. study, adds an article in The Conversation. The article cites studies with similar results from Switzerland and Australia that “also showed that most children recover fully from COVID-19.”

Optimal Oxygenation: Preventing Organ Dysfunction

Little difference was noted between the effect of low- vs. high-normal oxygenation targets.

Targeting oxygen therapy at a low-normal range for critically ill patients does not significantly reduce organ dysfunction compared with high-normal targets, according to a trial with 400 patients.

Effect of Low-Normal vs High-Normal Oxygenation Targets on Organ Dysfunction in Critically Ill Patients: A Randomized Clinical Trial,” in JAMA: The Journal of the American Medical Association, also finds no significant differences in duration of mechanical ventilation or in-hospital mortality among patients receiving the two therapies. The clinical trial acknowledges, however, that it “may have had limited power to detect a smaller treatment effect than was hypothesized.”

The trial enrolled adult patients (median age 68) with at least two positive criteria for systemic inflammatory response syndrome at four ICUs in the Netherlands from February 2015 to October 2018. A total of 205 patients were randomized to receive low-normal partial pressure of oxygen (PaO2) at 8 to 12 kPa (60-90 mm Hg), while 195 patients received high-normal targets of 14 to 18 kPa (105-135 mm Hg).

Using the Sequential Organ Failure Assessment (SOFA) scale, the trial ranked non-respiratory organ failure among participants during the first 14 days — with lower scores indicating less severity. In the low-normal oxygenation group, the median SOFA rank was -35 points compared with -40 points in the high-normal group, not a significant difference, the trial adds.

Citing an editorial accompanying the trial, an article in Physician’s Weekly notes the trial did not “provide the definitive answer on the optimal targets for oxygen therapy and will not change clinical practice.”

Beta-Blocker Beneficial in Small Trial of Patients With COVID-19 and ARDS

Metoprolol, inexpensive and widely available, improved respiratory function.

Metoprolol seemed effective for treating alveolar inflammation and respiratory function in patients with severe COVID-19-associated acute respiratory distress syndrome (ARDS).

According to “Metoprolol in Critically Ill Patients With COVID-19,” in Journal of the American College of Cardiology, the small randomized pilot trial produced no adverse effects and improved oxygenation in patients undergoing invasive mechanical ventilation. Repurposing metoprolol for the treatment of COVID-19–associated ARDS “appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.”

The trial — which included 12 patients on metoprolol and a control group of eight — was conducted at a single site in Madrid, Spain, between October 2020 and January 2021. Patients who received three days of intravenous metoprolol had a nonsignificant reduction in number of days in the ICU and less time on mechanical ventilation through “the attenuation of infiltration by immune cells, especially neutrophils, and reduced levels of their related pro-inflammatory and NETosis byproducts.”

Because the beta-blocker metoprolol is inexpensive, widely available and helps reduce exacerbated inflammation in patients with myocardial infarction, the trial recommends corroborating the data in a larger population. “Given that neutrophils play a major role in the pathophysiology of ARDS of many causes (not only COVID-19 related), further large validation studies might include a wide spectrum of patients with this condition,” the trial adds.

Limitations include the small sample size, the trial being conducted at one center and possible “selection bias resulting in patients with very poor condition according to physicians not considered for inclusion.”

President’s Column: Giving Meaning to Our Recognition

What does meaningful recognition look and feel like right now? In Beth Wathen’s latest column, she shares how valuable recognition is, and how important it is during these times to explore where our colleagues are, acknowledge their feelings and learn what meaningful means to them.

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Nurse Story: A Test of Teamwork

On a flight to a well-deserved Hawaiian vacation, three NICU nurses were called upon to help in the birth and care of a premature baby and his mother. They sprang into action and they delivered! Read their exciting tale.

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