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: Acute Ischemic Stroke – Spoon-Feed Version

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No matter what you think about tPA (alteplase), this is a quick clinical practice summary to consider when you are taking care of your next stroke patient.

Why does this matter?
Stroke is common; 700,000 ischemic strokes occur in the U.S. each year. Thrombolytics and mechanical thrombectomy have opened up new, and sometimes, controversial treatments for stroke. Let’s see how this NEJM author summed this up.

Stroke step-by-step

  1. Opening gambit: ABCs, check glucose

  2. Determine: Time of onset (last known normal, LKN), NIHSS (NIH stroke scale), pre-morbid function (modified Rankin Scale, mRS)

  3. Initial imaging of choice: CT head non-contrast to rule out bleed and calculate ASPECTS score.

  4. Time from onset: 0-6 hours

    1. Disabling stroke (NIHSS ≥ 6) and within 4.5h -> IV tPA if eligible

      1. Get CTA/MRA if you have the capability. If unable, transfer to a facility with capability to perform mechanical thrombectomy.

    2. If ineligible for tPA – consider potential mechanical thrombectomy (NIHSS ≥ 6, ASPECTS ≥ 6).

    3. Give tPA if eligible, even if mechanical thrombectomy is still under consideration

  5. Time from onset: 6-24 hours

    1. Perform CTA or MRA for potential thrombectomy if they meet either of the following.

      1. DEFUSE 3 Criteria: NIHSS ≥ 6; LKN between 6-16h; internal carotid or proximal middle cerebral artery (MCA) occlusion; infarct volume <70 mL, ratio of ischemic tissue to initial infarct volume ≥1.8, and absolute volume of penumbra ≥15mL on CT perfusion or MRI diffusion/perfusion.

      2. DAWN Criteria: LKN between 6-24h; internal carotid or first segment MCA; clinical deficits greater than infarct volume: ≥80 y NIHSS ≥10 and infarct <21mL OR <80y NIHSS ≥10 and infarct <31mL OR <80y NIHSS ≥20 and infarct 31 to <51mL.

  6. For patients who do not fit in the previous criteria

    1. < 24 hours

      1. NIHSS ≤ 3

        1. 21 day course of clopidogrel + aspirin (if no contraindications) within 24h of onset

    2. > 24 hours

      1. Daily aspirin (if no contraindications) within 48h of onset

  7. Considerations

    1. There may be a role for tPA at 4.5-9h if thrombectomy is unavailable and there is a large penumbra to core ratio (> 1.2, infarct core volume < 70mL) on CT perfusion study or MR perfusion.

Acute Ischemic Stroke. N Engl J Med. 2020 Jul 16;383(3):252-260. doi: 10.1056/NEJMcp1917030.

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#2: Musculoskeletal Pain – New ACP | AAFP Guidelines

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Topical NSAIDS (with or without menthol), followed by oral NSAIDs or acetaminophen, should be used to treat non-low back musculoskeletal pain in adults. Opioids, including tramadol, are not recommended. 

Why does this matter?
If you are an adult, chances are you have had musculoskeletal pain. 15% of all emergency department visits and 4% of all healthcare visits are for MSK pain. There are many options for treating acute MSK pain, and we must determine which interventions are both effective and safe.

My doctor nSAID this was the best medicine
Using a systematic review that looked at 207 studies evaluating 32,959 patients with acute (<4 weeks) non-low back MSK pain and another systematic review that looked at predictors of prolonged opioid use after MSK injury, clinical recommendations were published by the American College of Physicians and the American Academy of Family Physicians. Looking for the optimal combination of pain relief, physical function, treatment satisfaction, and adverse events, the following recommendations were made.

Recommendation 1: First-line therapy should be with topical NSAIDs with or without menthol gel. Strong recommendation; moderate-certainty evidence – With generic topical diclofenac now being available without prescription, this recommendation is easier to follow more than ever.

Recommendation 2a: Treat with oral NSAIDs or oral acetaminophen. Conditional recommendation; moderate-certainty evidence. – Oral NSAIDs come with increased risk of GI adverse effects when compared to topical gel. Be clear in your discharge instructions when advising use of oral NSAIDs.

Recommendation 2b: Specific acupressure or transcutaneous electrical nerve stimulation can be used to help with physical function and reduce pain. Conditional recommendation; low-certainty evidence.

Recommendation 3: They suggest against treating with opioids, including tramadol. Conditional recommendation; low-certainty evidence. – No opioids in any review achieved greater benefit than NSAIDs, and opioids caused the most harm.

Despite these recommendations, and most control participants having statistically significant pain relief by 1-7 days, even the best supported interventions reported only modest benefits. Here, just like in all patients, it is important to set expectations.

Nonpharmacologic and Pharmacologic Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries in Adults: A Clinical Guideline From the American College of Physicians and American Academy of Family Physicians. Ann Intern Med. 2020 Aug 18. doi: 10.7326/M19-3602. Online ahead of print.

Management of Acute Pain From Non-Low Back Musculoskeletal Injuries: A Systematic Review and Network Meta-analysis of Randomized Trials. Ann Intern Med. 2020 Aug 18. doi: 10.7326/M19-3601. Online ahead of print.

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#3: Early Norepinephrine for Septic Shock

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Early initiation of norepinephrine for patients with septic shock was associated with decreased short-term mortality, reduced time to achieve target MAP, and lower volume of IV fluid administered within 6 hours.

Why does this matter?
There have been several advances in management of sepsis, but septic shock continues to be a leading cause of morbidity and mortality. The 2018 Surviving Sepsis Campaign Bundle recommends administering broad-spectrum antibiotics, rapidly administering 30 ml/kg crystalloid for hypotension or lactate ≥ 4 mmol/L, and applying vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain MAP ≥ 65 mmHg. Recent guidelines have also recommended norepinephrine as the first-line vasopressor for septic shock. CENSER showed improved shock control with early norepinephrine and was included in this meta-analysis. However, optimal timing of vasopressors, especially in relation to IV fluid administration, is unknown.

Norepinephrine for septic shock – use early and often
This was a systematic review and meta-analysis of 5 studies with 929 patients comparing early vs late norepinephrine initiation for patients with septic shock. Patients receiving early norepinephrine had lower short-term mortality (21.6% vs. 37%; OR = 0.45, 95%CI 0.34 to 0.61), shorter time to achieve target MAP (mean difference = − 1.39 hour; 95%CI, − 1.81 to − 0.96), and less IV fluids within 6 hours (mean difference = − 0.50L; 95%CI − 0.68 to − 0.32). There was no statistically significant difference in ICU length of stay.

Unfortunately, there was not a standard definition of “early” vs “late” norepinephrine initiation between the included studies. The classification of “early” norepinephrine initiation ranged from within 1 hour to within 6 hours. However, regardless of the exact timing of the “early” groups, this review suggests that early and aggressive initiation of norepinephrine can improve outcomes for patients in septic shock.

Of note, peripheral IV norepinephrine infusion, which is safe when administered with proximal large bore IVs at low doses for short time periods, can help facilitate more rapid administration of vasopressors for patients with septic shock.

We may have to wait for the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) study for the definitive answer about early IV fluids vs early vasopressors for septic shock. But in the meantime, consider early initiation of norepinephrine for patients with septic shock, especially when their blood pressure does not rapidly improve with initial IV fluid administration.

Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis. Crit Care. 2020 Aug 6;24(1):488. doi: 10.1186/s13054-020-03204-x.

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