Journal Feed Weekly Wrap-Up

We always work hard, but we may not have time to read through a bunch of journals. It’s time to learn smarter. 

Originally published at JournalFeed, a site that provides daily or weekly literature updates. 

Follow Dr. Clay Smith at @spoonfedEM, and sign up for email updates here.


#1: Diltiazem vs Metoprolol for A-fib with RVR – Meta-analysis

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IV diltiazem has higher efficacy, shorter average onset time, and lower ventricular rate for treatment of atrial fibrillation with rapid ventricular rate (AF RVR) compared to IV metoprolol, with no increase in adverse events.

Why does it matter?
The incidence of atrial fibrillation is increasing, and atrial fibrillation is the most commonly encountered arrhythmia in the emergency department. Patients presenting with AF RVR require prompt treatment in the emergency department. IV diltiazem and metoprolol are two of the most common agents used to treat this arrhythmia in the ED. We’ve covered this before, but this meta-analysis helps us take a big-picture view.

Slow down heart
IV diltiazem and metoprolol are two common agents used to treat AF RVR in the emergency department. This meta-analysis pooled results from 17 studies, involving 1,214 patients, to assess efficacy and safety of these agents.

The pooled results showed the following:

  • Efficacy: IV diltiazem was superior to metoprolol; RR=1.11 (95%CI 1.06 to 1.16, P<0.00001) at 30 and 60 minutes. No statistically significant difference found at 10, 90 or 120 minutes.

  • Time of onset:  significantly shorter for IV diltiazem compared to metoprolol; weighted mean difference: -1.13 (95%CI -1.97 to 0.29, P=0.009).

  • Decrease in ventricular rate: IV diltiazem was superior to metoprolol for ventricular rate at 5, 10, 15, 30, 60, and 90 minutes, but no significant difference was found at 120 minutes.

  • Blood pressure: No statistically significant difference in systolic blood pressure between the two groups at 5, 10, or 30 minutes; IV metoprolol decreased systolic blood pressure compared to diltiazem at 15 minutes. There was no statistically significant difference in diastolic blood pressure.

  • Adverse events: no statistically significant difference between the two groups

So, what? This study suggests that while efficacy is similar at 120 minutes, IV diltiazem works more quickly than IV metoprolol for treatment of AF RVR in the ED.

As always, remember to use caution with rate-controlling agents in patients with secondary causes of AF RVR (e.g. ischemia, metabolic or endocrine abnormalities, pulmonary embolism, heart failure or sepsis), and be sure to treat the underlying cause.

Source
Intravenous diltiazem versus metoprolol for atrial fibrillation with rapid ventricular rate: A meta-analysis. Am J Emerg Med 2022 Jan; 51: 248-256. Doi: 10.1016/j.ajem.2021.08.082. Epub 2021 Nov 6


#2: MOVe-Out RCT | Molnupiravir for COVID-19 in Outpatients

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Molnupiravir is an oral antiviral drug that has been shown to decrease risk of hospitalization or death at 29 days in patients with mild to moderate COVID-19 who are at risk for progression to severe disease.

Why is this important?
As the pandemic continues, we continue to seek effective treatments for COVID-19, and this trial studied the efficacy and safety of molnupiravir as an agent to treat outpatients with mild to moderate COVID-19 at risk of progression to severe disease.

MOVe-Out COVID?
Molnupiravir is a nucleoside analog that inhibits SARS-CoV-2 replication and increases mutations in viral RNA. The MOVe-Out Trial was a phase 3, double-blind randomized controlled trial that evaluating efficacy and safety of treatment with molnupiravir started within 5 days of symptom onset. The trial included non-hospitalized, unvaccinated adults with mild to moderate, Covid-19 with at least one risk factor for progression to severe disease. These included age > 60 years, active cancer, chronic kidney disease, COPD, obesity (BMI ≥30), serious heart conditions, diabetes mellitus.

The trial excluded pregnant women or those unwilling to use contraception during the intervention and 4 days after completion, patients on dialysis or with GFR< 30 ml/min/1.73 m2, severe neutropenia, thrombocytopenia or COVID-vaccinated patients.

The primary outcome was a composite of hospitalization for any cause ≥24 hours and death within 29 days. In the treatment group, 6.8% were hospitalized or died through day 29 vs 9.7% in the placebo group with treatment difference of 2.9% (95% CI, -5.9 to -0.1). The number needed to treat was 34 patients. This was lower than the treatment difference in the interim analysis (7.3% vs 14.1%). Secondary analyses (in the supplement) showed that the molnupiravir group had improvement in WHO Clinical Progression Scale by day 5, lower likelihood of symptom progression, and larger reduction in viral load at days 3 and 5. There was no statistically significant difference in adverse events.

The big picture: Molnupiravir has been shown to have lower efficacy than other agents that have been studied, such as Paxlovid, and the FDA has approved this as a therapeutic option when other FDA-authorized treatments are not available (see NIH guidelines here).

In addition, molnupiravir is believed to be a teratogen (see FDA Fact Sheet), and patients should use a reliable form of contraception (females: during treatment and for 4 days after; males: for at least 3 months after treatment), which raises some concern for compliance.

Source
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med 2022 Feb 10; 386(6): 509-520. Doi: 10.1056/NEJMoa2116044. Epub 2021 Dec 16.

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The PLUS (Plasmalyte 148 vs saline) trial found no evidence that the risk of death or acute kidney injury was higher in critically ill adults who received normal saline compared to those who received balance multielectrolyte solution (BMES).

Why is this important?
IV fluids are a key component of resuscitation and treatment of critically ill patients. There have been increasing concerns that the use of normal saline may increase risk of acute kidney injury and death compared to BMES and several recent studies comparing BMES and saline, with conflicting results: SMART, SALT-ED, and BaSICS.

Another round for saline vs. balanced fluids…
The PLUS trial was a double-blind, multicenter, randomized controlled trial in which 5,037 critically ill patients were assigned to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the ICU, followed for 90 days. Baseline characteristics of the two groups were well-matched. The median volume of trial fluid administered was 3.9 L (higher than some other studies).

There was no statistically significant difference in the primary outcome of death within 90 days of randomization in the BMES group compared to the saline group (21.8% vs 22.0%, 95% CI -3.6 to 3.3; P=0.90). The use of saline resulted in significantly higher serum chloride and lower pH compared to BMES, but there was also no significant difference between the two groups with regards to secondary outcomes of initiation of new renal replacement therapy (12.7% vs 12.9%, 95%CI -2.96 to 2.56) or mean (±SD) maximum increase in serum creatinine (36.6±94.0 mmol/L vs 36.1±90.2 mmol/L). Subgroup analyses were conducted based on illness severity before randomization, presence of sepsis, kidney injury, age, sex, and ICU admission after surgery, and did not show a significant difference between the two groups.

The authors discuss the results of a concurrently published meta-analysis including their data which suggests there is a high probability that use of BMES reduces mortality in critically ill adults. This study estimated that the effect of BMES vs saline ranges from a 9% relative reduction to 1% relative increase in risk of death, suggesting a high probability that use of BMES reduces mortality. The authors also point out this probability was even higher in patients with sepsis and suggest that specific patient factors may inform fluid choice.

Given results of the concurrent meta-analysis including the study data, I will likely continue to favor BMES in critically ill patients without traumatic brain injury, though other factors such as cost and availability of fluids as well as drug compatibility may impact fluid choice as well.

Sources

Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med. 2022 Jan 18. doi: 10.1056/NEJMoa2114464. Epub ahead of print. PMID: 35041780.

Balanced Crystalloids versus Saline in Critically Ill Adults-A Systematic Review with Meta-Analysis. NEJM Evid 2022; 1(2). Doi: 10.1056/EVIDoa2100010

 

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