JournalFeed 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. 

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#1: LOWMAGHI – Magnesium for Afib Rate Control

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Among patients with atrial fibrillation with rapid ventricular response (RVR), low-dose magnesium (4.5g over 30 minutes) was an effective adjunct to standard therapy* compared to placebo and caused far fewer side effects than high-dose magnesium.

Why does this matter?

Magnesium seems to be indicated for almost everything: pre-eclampsia, hypokalemia, torsades, migraine, and asthma exacerbations. In atrial fibrillation, magnesium has been considered a potential therapy given it decreases automaticity and increases the refractory period of the AV node.  Prior studies have shown benefit of magnesium in addition to standard therapy, but the dose of magnesium administered varies considerably among studies.

MAGic Medicine for the Heart

This is a double blind RCT performed in three tertiary centers in Tunisia that enrolled 450 consecutive patients with rapid atrial fibrillation (HR > 120 beats/min). In addition to standard rate control therapy, patients received either low-dose magnesium (4.5g in 100cc NS), high-dose magnesium (9g in 100cc NS), or placebo (100cc NS) administered over 30 minutes. The primary endpoint was HR < 90 or drop in HR by 20% at 4 hours. Low-dose magnesium had a higher percentage of patients that achieved rate control compared to placebo (64% vs 43%, respectively, p < 0.05). There was no statistical difference in primary outcome between low dose (64%) and high dose (60%) magnesium although both statistically outperformed placebo. High dose placebo had significantly more adverse events, namely flushing, compared to both placebo and low dose magnesium.

*The big caveat to this study is that digoxin was the most used rate control agent (47.5%). A secondary analysis looking exclusively at magnesium as an adjunct to calcium channel blockers and beta blockers found outcomes consistent with the overall results although the study author states the secondary analysis was not statistically significant.

Source

LOw dose MAGnesium sulfate versus HIgh dose in the early management of rapid atrial fibrillation: randomised controlled double blind study.  Acad Emerg Med. 2018 Jul 19. doi: 10.1111/acem.13522. [Epub ahead of print]

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Another Spoonful

ALiEM posted a review of the literature a couple years back.

#2: LR vs NS for Pediatric DKA

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Use of any LR in pediatric patients with DKA, as opposed to only NS, was associated with lower overall costs, similar length of stay, and markedly reduced incidence of cerebral edema in this retrospective study.

Why does this matter?

Given the results of the SMART and SALT-ED trials, balanced crystalloids appear to be better for patients.  We also know that rate of fluid administration and use of 1/2NS compared with NS did not make a difference in cerebral edema for pediatric patients with DKA.  How does use of NS or LR impact pediatric DKA

LR wins again

This was a retrospective review of a large pediatric health database that reviewed over 45,000 cases of pediatric DKA.  Only 4% received only LR, while 8% received both NS and LR.  The remaining 88% received NS.  They found that use of any LR was associated with lower overall costs, similar length of stay, and markedly reduced incidence of cerebral edema.  Over the study period, NS was increasingly used, likely a result of guidelines based on expert opinion that recommended NS.  And as NS use increased, so did the incidence of cerebral edema.  Firm conclusions cannot be drawn from a retrospective study with innumerable potential confounders, but taken in light of the recent SMART and SALT-ED trials, it suggests a switch to LR or other balanced crystalloid may improve outcome for children with DKA.

Source

Resuscitation With Ringer’s Lactate Compared With Normal Saline for Pediatric Diabetic Ketoacidosis.  Pediatr Emerg Care. 2018 Jul 16. doi: 10.1097/PEC.0000000000001550. [Epub ahead of print]

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#3: Lytics for Mild Stroke Disastrous

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Not surprisingly, patients with mild, non-disabling stroke did not benefit from receiving alteplase over aspirin.  If anything, the trend favored aspirin.  Five patients (3.2%) who received alteplase had intracranial hemorrhage (see example figure).

Why does this matter?

I’m not even going to get into the tPA debate here.  Most prior lytic studies excluded patients with mild neurological deficits from getting thrombolytic agents.  Why give a potentially dangerous drug and risk a major bleed when the stroke is not disabling?  Why indeed?

Remind me why this was a good idea?

This was a RCT of 313 patients with mild, non-disabling stroke, NIHSS 0-5.  The original study protocol called for an enrollment of 948.  The study was funded by Genentech and, “was terminated due to slow enrollment.”  Authors noted, “This was a financial decision,” by Genentech and that, “The academic members of the steering committee recommended against termination but accepted this financial decision by the sponsor.”

Patients were randomized to receive standard dose alteplase (tPA) and oral placebo or aspirin 325mg orally and IV placebo.  They found no statistical difference in the primary outcome (modified Rankin Scale score 0-1) at 90 days, though the trend favored the aspirin group; 78.2% of patients had a good outcome in the alteplase group vs 81.5% in the aspirin group.  Again, this was not statistically significant.  There was a statistically significant increased risk of symptomatic intracranial hemorrhage in the alteplase group, 3.2% (5 patients) vs zero in the aspirin group.  Serious adverse events were double in the alteplase group vs aspirin: 26% vs 13%.  The authors concluded, “the very early study termination precludes any definitive conclusions, and additional research may be warranted.”

Really?  These patients had mild strokes; half got alteplase anyway, and five of them had a head bleed as a result.  Can anyone tell me why this study was a good idea?  It raises serious questions about the safety of “additional research.”  My vote is a firm NO.

Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial.  JAMA. 2018 Jul 10;320(2):156-166. doi: 10.1001/jama.2018.8496.

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