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LR or NS for Sickle Cell Pain Crisis?

October 11, 2024

Written by Megan Hilbert

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For sickle cell patients (particularly Hgb SS) with a vaso-occlusive episode (VOE), large volume resuscitation (>2L) with lactated ringers (LR) has been shown to have improved outcome measures compared to normal saline (NS).

Another ding against NS
Preclinical research has demonstrated that NS can promote erythrocyte sickling and endothelial adhesion of circulating erythrocytes – effectively worsening the microvascular environment in a VOE. Patients presenting with VOE often are hypovolemic from decreased PO intake or losses from vomiting and diarrhea. As such, it is necessary to volume resuscitate and prevent worsening metabolic acidosis. This large multicenter US cohort target trial emulation study* was aimed to determine if the number of hospital-free days (HFD) by day 30 differed among patients resuscitated with LR versus NS on hospital day 1.

The authors found that patients who received LR had more HFDs (marginal mean difference 0.4, 95%CI 0.1-0.6 days). Secondary measures were often in favor of LR as well with patients having shorter hospital lengths of stay (marginal mean difference -0.4, 95%CI -0.7 to -0.1 days), more intravenous opioid-free days (marginal mean difference 0.4, 95%CI 0.1-0.6 days), and lower risk of 30-day readmission (marginal mean difference -5.8%, 95%CI -9.8% to -1.8%). That said, these results tended to be heterogenous and the statistical significance held only when the patient received more than 2L of volume resuscitation on hospital day 1 and in patients with HbSS genotype. There was no difference in organ support-free days, blood transfusion-free days, hospital mortality, or intravenous diuretic use between the two fluid types.

Therefore, in patients with HbSS genotype and/or resuscitated with greater than 2L of fluid on hospital day 1, LR tended to show improved outcomes as compared to NS.

*Never heard of targeted trial emulation before? You’re not alone. The moral is: The authors completed an observational study but set it up in a way that mimicked a randomized control trial to minimize bias often found in observational design (ie selection bias).

How will this change my practice?
In general, I reach for LR far more than NS, particularly in large volume resuscitation. This study continues to support my practice of reaching for LR first.

Source
Lactated Ringer vs Normal Saline Solution During Sickle Cell Vaso-Occlusive Episodes. JAMA Intern Med. 2024 Sep 9:e244428. doi: 10.1001/jamainternmed.2024.4428. Epub ahead of print. PMID: 39250114; PMCID: PMC11385329.

2 thoughts on “LR or NS for Sickle Cell Pain Crisis?

  • This is great. I wasn’t aware of the sickling events with normal saline. At my shop we mostly use plasmalyte as a balanced fluid. Any thoughts on plasmalyte as opposed to LR?

    • Rosny, so great to hear from you! This LR study was the first I had seen about this, and I have not seen other studies about Plamalyte for sickle cell anemia patients with pain crisis. However, this in vitro study found increased hemolysis in sickled cells with NS vs. Plasma-Lyte A: https://pubmed.gov/30937917. I’ll keep my eye out for anything, and if you run across any articles, just shoot me the PMID number, and we will cover it.

What are your thoughts?