CLINICAL

ED Patients With Gout Flares Too Often Receive Opioids

Patients with gout flares presenting to the emergency department (ED) are often given opioids or discharged with opioids, even though the pain relievers are not recommended in treatment guidelines, New Jersey researchers report.

Reviewing 214 patient records from the ED with gout at Robert Wood Johnson University Hospital in Somerset, investigators found that 51 patients (24%) were discharged on opioids, and that about 82% of patients had their first encounter with opioids due to this visit.

In the ED, opioids (28%) were used second only to nonsteroidal anti-inflammatory drugs (NSAIDs; 41.6%). At discharge, opioids (23.9%) were the third most common medication prescribed, after NSAIDs (37%) and steroids (34.6%), the investigators reported at the American College of Clinical Pharmacy’s 2020 virtual poster symposium (poster 348).

Best practices for gout flare management in the ED are urgently needed, said senior author Luigi Brunetti, PharmD, an associate professor of pharmacy practice and administration at Rutgers University’s Ernest Mario School of Pharmacy, in New Brunswick.

Dr. Brunetti said he had been collaborating with rheumatologist Naomi Schlesinger, MD, on a few gout-related projects when they noted patients being discharged from the ED on opioids and decided to study it further. “That’s when we identified these trends in drug use that had us scratching our heads,” Dr. Brunetti said. “It’s one thing if you have a patient coming in on an opioid, perhaps for another indication. But we had a significant percentage of patients that were sent home on an opioid who previously were not prescribed one.”

The study pulled records from all patients visiting the ED with a primary diagnosis of gout from Jan. 1, 2016, through July 1, 2019. They used a comparative analysis to determine differences between patients who were or were not discharged on opioids, and multivariable logistic regression to identify factors associated with an opioid prescription upon discharge from the hospital.

Moreover, 12% of patients were discharged on opioids without anti-inflammatory drugs, and a history of opioid use (odds ratio [OR], 3.3; 95% CI, 1.3-8.6; P=0.14) and gastroesophageal reflux disease (OR, 3.5; 95% CI, 1.09-10.9; P=0.035) was associated with opioid prescription upon discharge. Medications prescribed in the ED and upon discharge were NSAIDs, corticosteroids, opioids, acetaminophen and colchicine.

“There’s a good frequency of inappropriate prescribing of opioids for gout flares, and it’s good the authors have statistics to make a case for better education of gout management,” commented Cortney Mospan, PharmD, an assistant professor of pharmacy at Wingate University Levine College of Health Sciences, in Wingate, N.C. Dr. Mospan co-authored a recent continuing education article on the pharmacist’s role in managing gout and hyperuricemia (bit.ly/2UD554C).

What the Guidelines Say

This spring, the American College of Rheumatology released the 2020 Guideline for the Management of Gout, Dr. Mospan said. There are three foundational drugs recommended for flares: NSAIDs, corticosteroids and colchicine.

A gout flare indicates that uric acid has elevated to the point that it exceeds the ability to be absorbed, and crystals start to form, she noted. The body recognizes these crystals as foreign substances, which activates the immune system to attack and eliminate them.

“When you look at treatment options recommended by the guidelines, those are all anti-inflammatory medications as opposed to a pain medication like opioids, because what we need to be doing in that acute gout flare—even though there is a tremendous amount of pain—is to decrease that inflammatory response,” Dr. Mospan said. “That will result in pain relief and subside that acute gout flare.”

There’s another reason to treat that inflammation, she added. Studies have shown a connection between elevated uric acid and cardiovascular disease, including hypertension ion and diabetes (N Engl ngl J Med 2008;359[17]: 7]: 1811-1821).

Prescribing opi- oids is problematic not only because the drugs do noth- ing for the underlying ng inflammation; opioids ds also can introduce ce patients—who haven’t n’t been exposed before— e— to the addictive painnkillers, Dr. Mospan an said. Moreover, leftover pills could be diverted by the patient or a visitor to the home, increasing the supply of illicit opioids in the community.

Pharmacists can play a key role in gout treatment, Dr. Mospan said, including educating patients on medication benefits and side effects and the importance of adherence. They also can help prescribers adhere to treatment recommendations.

Based on the Rutgers study, such help is sorely needed. Aside from the high percentage of opioid prescriptions, the investigators also found that about 30% of patients were prescribed acetaminophen, which is not recommended and will not help with pain. —Karen Blum

The sources reported no relevant fi nancial relationships.

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Steroids Calm Storm

continued from page 1

the department head and a professor of pharmacy practice at the University of Connecticut School of Pharmacy, in Storrs. Dr. White, a member of the Pharmacy Practice News editorial advisory board, was not part of the studies but has conducted systematic reviews into other treatment options for COVID-19 and was asked to comment.

The meta-analysis reviewed seven randomized clinical trials from 12 countries with a total of 1,703 critically ill patients with COVID-19 comparing corticosteroids with the standard of care. The trials studied three different corticosteroids—dexamethasone, hydrocortisone and methylprednisolone—and the authors analyzed the results of the RECOVERY, REMAPCAP, CoDEX, CAPE COVID and three additional trials. The primary end point was risk for death after 28 days. Fewer people receiving any type of systemic steroid died (222/678; 33%) than those who did not receive steroids (425/1,025; 41%) (JAMA 2020 Sep 2. [Epub ahead of print]; bit.ly/32AW6Fb). Dexamethasone had the largest populations studied and was the only steroid with significant survivcondition.’ al benefits in a subgroup analysis (36% reduction in odds), but hydrocortisone had almost the same reductions in odds (31%) and just missed significant findings. Methylprednisolone was only assessed in a single small trial, and the odds reduction was a nonsignificant 9%, but with a very large confidence interval.

The meta-analysis helped to clarify whether the benefit from steroids seen in the earlier RECOVERY trial was due to just dexamethasone, but this pooling of data seems to point to the efficacy of other steroids, according to Steven J. Martin, PharmD, BCPS, the dean and a professor of Ohio Northern University Rudolph H. Raabe College of Pharmacy, in Ada. Dr. Martin did not participate in the studies.

“I believe the RECOVERY trial’s use of dexamethasone led to the early speculation that that drug may be preferred, but the other two trials with hydrocortisone and methylprednisolone also demonstrated positive benefits. Thus, at this point, one would conclude that this is a class effect,” explained Dr. Martin, also a mem

The CoDEX trial supporting the use of dexamethasone was performed in Brazil. This open-label, multicenter, randomized clinical trial of 299 patients with COVID-19 and moderate or severe acute respiratory distress syndrome compared IV dexamethasone plus standard of care with standard of care alone. They saw a statistically significant increase in the number of days patients were alive and free from mechanical ventilation. The dexamethasone group had a mean of 6.6 days off the ventilator (95% CI, 5.0-8.2) versus four days in the standard-of-care group (95% CI, 0.2-4.38; P=0.04), but there was no mortality difference between both groups (JAMA 2020 Sep 2. [Epub ahead of print]; bit.ly/3c3j378).

An international group in the REMAPCAP trial looked at whether hydrocortisone also had promising effects on critically ill patients with COVID-19 (JAMA 2020 Sep 2. [Epub ahead of print]; bit.ly/2RAacjU). In the randomized hydrocortisone study, 403 patients with suspected or confirmed COVID-19 who

‘We have learned in other disease states that steroids have a clearly demarcated role in managing systemic inflammation without worsening the underlying

ber of the PPN editorial advisory board.

required respiratory or cardiovascular —Steven J. Martin, PharmD organ support, such as mechanical ventilation or drugs to support their blood pressure, were enrolled between March and June 2020. The cohort included patients of mixed ethnicities in Australia, Canada, France, Ireland, the Netherlands, New Zeland, the United Kingdom and the United States. One group was treated with a fixed dose of 50 mg of hydrocortisone four times per day for seven days; another group was treated with hydrocortisone only if their blood pressure dropped; and a third group received no hydrocortisone.

The results showed that using the fixed dose of hydrocortisone led to a 93% chance of a better outcome—greater chance of survival and less need for organ support—than not using hydrocortisone. If the hydrocortisone was given only when the blood pressure was low, the chance of a better outcome was 80%. This study stopped recruiting patients early after the RECOVERY trial published data in early June, suggesting dexamethasone boosted recovery (N Engl J Med 2020 Jul 17. [Epub ahead of print]. doi: 10.1056/NEJMoa2021436).

“The data seemed clearest for

Fixed-dose hydrocortisone led to a 93% chance of survival and less need for organ support than not using the steroid.

dexamethasone, but in totality they all worked,” said Shmuel Shoham, MD, an associate professor of medicine at the Johns Hopkins University School of Medicine, in Baltimore. Dr. Shoham was not part of the studies but has been involved in other trials for COVID-19 and sits on the COVID-19 treatment guideline panel of the Infectious Diseases Society of America.

“That does not mean it is better than the other ones,” Dr. Shoham said. “If available, it might still make sense to use dexamethasone as a first option, but it looks like it is the class effect rather than individual corticosteroids that is important.”

Hydrocortisone has mineralocorticoid effects that produce a positive sodium balance and higher serum sodium concentrations, increased extracellular fluid volume, hypokalemia and alkalosis, Dr. Martin explained. “Expanded extracellular fluid is generally a good thing in shock, but alkalosis can worsen oxygenation if the pH becomes too high. Hypokalemia can cause heart rhythm disturbances if too low. Dexamethasone doesn’t have mineralocorticoid activities, and I can’t tell whether that was a good thing or bad thing in these studies.

“There are potency differences, but the dosing of the drugs was adjusted to account for those differences,” he said. “At this point, one would conclude this is a class effect.”

Dr. White agreed: “While dexamethasone has the strongest data set showing benefit, hydrocortisone is a very reasonable alternative. Methylprednisolone had too small a trial to make a meaningful determination of its efficacy; the 95% confidence interval was very wide. But in equipotent doses, there is reason to believe from other inflammatory diseases that methylprednisolone could also be an alternative if dexamethasone and hydrocortisone were unavailable.”

This is an important consideration because “dexamethasone was one of the drugs on back order and shortage since the initial RECOVERY trial results came out, so being able to diversify to other corticosteroids would help meet demand,” Dr. White explained.

Dosing seems to be an important consideration, according to Drs. White and Martin, and lower doses appear to be as effective as higher ones.

“I have to believe dose is important,” Dr. Martin said. “The dosing for the trials in the meta-analysis was varied. In trials that administered low doses of corticosteroids, the overall fixed-effect OR [odds ratio] was 0.61, and the corresponding absolute risk was 29% for lowdose corticosteroids versus an assumed risk of 40% for usual care or placebo. In trials that administered high doses of corticosteroids, the fixed-effect OR was 0.83, and the corresponding absolute risk was 36% for high-dose corticosteroids versus an assumed risk of 40% for usual care or placebo.”

Even the authors of the meta-analysis concluded that higher doses were not more beneficial than lower ones. Using lower doses could also help reserve the medication for more patients, according to Dr. White.

It’s important to advise people that all of the patients in these studies were critically ill and required some type of oxygenation, typically ventilator support, all three experts said.

There is little to support widespread use by mildly ill patients. “We have learned in other disease states that steroids have a clearly demarcated role in managing systemic inflammation without worsening the underlying condition,” Dr. Martin said. “Too much steroid can cause problems of its own.”

In its treatment recommendations, the WHO recommended against the use of steroids outside of critical patients.

“At the beginning of the year, at times, it felt almost hopeless, knowing that we had no specific treatments. It was a very worrying time. Yet less than six months later, we’ve found clear, reliable evidence in high-quality clinical trials of how we can tackle this devastating disease,” said Anthony Gordon, MD, FFICM, FRCA, the chair of anesthesia and critical care at the Imperial College London, who participated in the REMAP-CAP study. —Marie Rosenthal

Dr. Gordon reported receiving grants from the NIHR and the NIHR Research Professorship. Drs. Martin, Shoham and White reported no relevant fi nancial relationships.

Feeding and COVID-19

continued from page 1

to recover. Nine percent of the patients died; among those with NRS scores of 5 or higher, the mortality rate was 43% (JPEN J Parenter Enteral Nutr [Epub Jul 1, 2020]. doi:10.1002/jpen.1953).

Hence the push for more widespread nutrition screening in COVID-19 patients. Different countries have developed a variety of screening tools, but “as long as the tool has been validated for use in your patient population and setting,” the effort should yield positive results, Dr. Gramlich said. If the tool shows the patient is at risk for nutritional deficiencies, a dietitian or nutrition care provider can conduct a formal assessment to determine whether malnutrition is present, identify barriers to intake, and develop an individualized plan, she noted. If patients develop any additional risk factors for nutritional deficiencies, such as nausea or poor food intake, they should be screened again. No prolonged fasting. protein: 75-100 g per day.

“Screening is not a one-and-done process,” stressed Dr. Gramlich, who is also a professor of medicine in the Division of Gastroenterology at the University of Alberta, in Edmonton.

Jay Mirtallo, MS, RPh, BCNSP, a clinical practice specialist at ASPEN who did not participate in the webinar, echoed the importance of widespread screening, and agreed that using a validated screening tool is important. However, if pharmacists and other providers don’t have access to such a tool, he noted, simply asking whether patients experienced recent unexplained weight loss, or have food insecurity—such as trouble accessing or preparing food for themselves— could help identify people at risk.

“You need to screen them, and then you have to act on it right away, because malnourishment can happen really quickly,” Mr. Mirtallo told Pharmacy Practice News.

Given that urgency, a collaborative approach to nutrition support is key, Dr. Gramlich noted. Indeed, “nutrition care is a team sport,” she said. “It requires multidisciplinary, interdisciplinary care.”

Barriers to Nutrition Support

As for pharmacists’ role, in addition to screening, they can help recognize barriers to food intake, such as trouble breathing or nausea, which often have pharmacologic treatment options. For instance, around-the-clock antiemetic therapy “makes a huge difference” in improving food intake, she said, adding that pharmacists also should pay attention to patients’ use of opioids during their hospital stay, which can have a major impact on gastric emptying and appetite.

What’s more, as medication experts, pharmacists can provide information about drug–nutrient interactions or medication metabolic complications to the health care team, noted Phil Ayers,

6 Tips for Improving Nutrition In Hospitalized COVID-19 Patients

Consider around-the-clock antiemetics in patients with nausea; don’t settle for as-needed therapy if nausea is an issue. Avoid immobilization by getting patients up and out of bed. Involve patients in their care; explain their nutritional deficiencies and what they could mean to their recovery. Consider alternatives to opioids. Consider nutritional requirements for COVID-19 patients. Fluid: approximately 3 quarts/L per day; calories: 2,000-2,500 per day; PharmD, BCNSP, the chief of clinical pharmacy services and a nutrition support service pharmacist at Mississippi Baptist Medical Center, in Jackson, who did not participate in the ASPEN webinar. Pharmacists also “need to be able to advocate for patients,” Dr. Gramlich said. This may include protecting meal times, such as making sure patients aren’t taken for scans or other testing during lunch or dinner hours. Dietitians often can’t make rounds in hospitals every day, but pharmacists can; if they see something, they should say something, Mr. Mirtallo said, adding, “If nutrition care isn’t being considered on a daily basis, pharmacists need to speak up.” Pharmacists also can help identify and address the barriers that can prevent COVID-19 patients from meeting their nutritional needs, Dr. Gramlich said. For instance, once patients are discharged or recovering at home, they have to socially isolate, which makes it more difficult to get enough healthy foods to

Source: American Society for Parenteral and Enteral Nutrition (bit.ly/3hzj3Ne). support their potentially long recovery. “They can’t go to the store, and their family members, if exposed, may not be able to go to the store,” she explained.

If hospitalized, patients may have to contend with personal protective equipment (PPE), nausea, breathing difficulties and other issues that can impede food intake. There also can be difficulties in providing care: Hospital pharmacists and dietitians may, for example, have to deal with shortages in PPE and recommendations to minimize exposure, Dr. Ayers said. Indeed, having a patient be readily accessible for a complete nutrition assessment “is a major challenge for all involved in the treatment of COVID-19 patients,” he told Pharmacy Practice News. As a result, “many institutions are using other means to collect this information, such as calling patients, family members, using telehealth, electronic health record review and discussing with the nurse at bedside.”

Taken together, all of these interventions underscore how invaluable the nutrition care team can be, not only for COVID-19 patients, but for those hospitalized with any condition, Dr. Gramlich noted. That’s why she called nutrition experts the “unsung heroes” of health care. When a patient is strug

Source: ASPEN.

gling with maintaining adequate feeding, nutrition experts may not always be the first providers we turn to, “but they are a key aspect of recovery,” given how poorly hospitalized patients fare when malnourished, she noted (Lancet 2019;393[10188]:2312-2321).

Inflammation May Be the Key

Mr. Mirtallo said he suspects that once researchers learn more about COVID-19, they will discover that its effect on nutritional status “will be as big or bigger than it is for other diseases.”

As for possible mechanisms of action, “it’s still too early to know for sure,” he said. “It’s just too new.” But there is definitely a relationship between COVID-19 and nutrition, he stressed, because the virus creates widespread inflammation, which malnutrition can exacerbate (SN Compr Clin Med 2020;1-5. doi: 10.1007/ s42399-020-00410-0).

Regardless of how future studies on COVID-19 and nutrition pan out, there’s no doubt that nutrition care often is neglected, Mr. Mirtallo noted. “It slips through the cracks, because you’re focused on the disease and treatment for the disease, which is mostly drugs,” he said. But as Mr. Mirtallo has been reminding his students for 40 years, nutrition is a key aspect of pharmacologic management. “So you can’t really separate the two.”

Dr. Gramlich echoed the need for a more inclusive view of nutrition, particularly during the pandemic. “I actually see nutrition care in COVID-19 as a pillar of overall care,” she said. “That pillar of care should be applied to all patients. In the time of COVID-19, it’s even more important.” —Alison McCook

Dr. Gramlich reported fi nancial relationships with Abbott, Baxter, Fresenius Kabi and Takeda; Dr. Ayers with American Regent and Fresenius Kabi; and Mr. Mirtallo with Fresenius Kabi.