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This is an exciting week of primary literature, particularly as many large critical care trials were published in major journals despite being “negative studies.”  We are excited by this as, too often, we see “negative studies” discarded.  Further, these studies examined things some practices we seem to believe in: balanced crystalloids, apneic oxygenation (see Dr. Scott Weingart’s podcast on the FELLOW study), treating fever. We love that the Free Open Access Medical Education (FOAM) community and study authors are examining beloved practice and open to questioning the very things we believe in. Well done.

We cover two core content papers out by Dr. Paul Young (@dogICUma) in JAMA and NEJM this week. His trials are as clever as his Twitter handle.

SPLIT – The FOAM world has sung the praises of balanced fluids given they have more physiologic composition. The thought, as detailed in this post, is that 0.9% NaCl contains an ABnormally large amount of chloride which may cause a hyperchloremic metabolic acidosis. Prior literature suggests an increased incidence of kidney injury with saline compared with balanced solutions. Thus, Dr. Paul Young and colleagues sought to study this with the best trial, to date, on this topic.

  • Multicenter, blinded,  cluster-randomized, double-crossover trial of adult ICU patients receiving crystalloids randomizing patients to 0.9%NaCl or Plasma-lyte (balanced solution).
    • Sites used one fluid for seven weeks and then crossed over to the other fluid (labeled Fluids A and B).
  • Primary outcome: AKI according to the RIFLE criteria  within 90 days – no difference between groups.
    • 9.6% in Plasma-lyte group vs 9.2% in the saline group (absolute difference 0.4% [95% CI, −2.1%-2.9%]; RR, 1.04 [95% CI, 0.80-1.36]; P = .77)
  • Secondary outcomes: No difference in renal replacement therapy, ICU days, mechanical ventilation, or mortality
  • A few things to keep in mind:
    • 70% of patients were admitted to the ICU from the OR (mostly cardiac surgery) and only ~15% from the ED
    • Patients got a median of 2L (1L -3.5L) of the study fluid, that’s it. These were not large volume resuscitations.
    • 90% of patients received fluids prior to enrollment, 60% got balanced crystalloid and only 30% 0.9% NaCl.

HEAT – We can’t help treating fever. We like the numbers euboxic, elevated temp? It must be bad! Doctors, parents, nurses treat fever reflexively.  Yet, there’s a thought that fever may be evolutionary and could potentially be protective. Treating pain or discomfort? That’s one thing, but here the authors sought to determine if there was a clinically important benefit to treating the number in ICU patients.

  • Randomised controlled, double blinded study of n=690 ICU patients with T>38F + suspected infection randomized to receive either 1 g paracetamol (acetaminophen/APAP) or placebo every 6 hours.
  • Primary outcome: median ICU-free days to day 28 – no difference 23 (IQR 13-25) in paracetamol group vs 22 in placebo group (IQR 12-25); P=0.07
  • No difference in secondary outcomes of mortality at 28 and 90 days
  • Limitations: ~30% of patients in both arms received open label APAP after the course of the study drug

Bottom Line Pearls:

  • It appears we may be SPLITting hairs over fluid choices. Giving a couple of liters? Fluid choice may not matter. SPLIT does not provide literature for larger volume resuscitations.
  • Treating fever in ICU patients with suspected infection doesn’t have an effect on ICU free days. Treat discomfort and pain with APAP but don’t expect to save lives or ICU beds by doing so.
  • “Negative studies” are important. So is examining our practice.
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