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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.

Source
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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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.

Source
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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