Written by Aaron Lacy
In children with CNS infections leading to increased intracranial pressure (ICP), treatment with hypertonic saline (3%) had better outcomes than 20% mannitol.
Why does this matter?
Three fourths of comatose children with acute CNS infections have increased ICP. Targeting and maintaining ICP < 20mm Hg is associated with increased survival in this population. There are several agents we can use to treat elevated ICP, and we need to know which one gives these patients the best chance of survival.
Pass me the salt
This open label RCT assigned children with acute CNS infections aged 1-12 with a GCS of ≤ 8 to either treatment with 3% hypertonic saline (n = 29) or 20% mannitol (n = 28). Primary outcome, an average ICP <20 over 72 hours (measured via intraparenchymal catheter), was seen in 79.3% of children treated with 3% compared to 53.6% in the mannitol group, adjusted HR 2.6 (95%CI 1.23-5.61). Additionally, 3% showed an increase in cerebral perfusion pressure (CPP) (15.4 vs 6 mm Hg, p = 0.007), higher modified GCS at 72 hours (median 10 vs 7, p = 0.003), lower mortality (20.7% vs 35.7%, p = 0.21), shorter duration of mechanical ventilation (5 vs 15 days, p = 0.002), shorter PICU stay (11 vs 19 days, p = 0.016), and less neurodisability at discharge (31% vs 61%, p = 0.049).
While data is less clear in traumatic cases of elevated ICP, this study’s results are compelling and are consistent with a prior RCT. The next time I see a child with increased ICP, I likely will be reaching for 3% as my first pharmacologic intervention. See the comment from Dr. Michael Wolf below on what he thinks of this study.
Randomized Clinical Trial of 20% Mannitol Versus 3% Hypertonic Saline in Children With Raised Intracranial Pressure Due to Acute CNS Infections. Pediatr Crit Care Med. 2020 Sep 29. doi: 10.1097/PCC.0000000000002557. Online ahead of print.
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This is expert commentary to help you go deeper on this topic.
”Much of what we know about treating elevated ICP comes from the TBI literature. The mechanisms are interesting and important: it is likely all about brain perfusion. It is worth noting that both mannitol and 3% saline work by decreasing blood viscosity, which leads to an autoregulation-induced vasoconstriction allowing for relatively constant cerebral blood flow despite reduced cerebral blood volume – hence a fast decline in ICP if intracranial compliance is poor. The osmotic effects are slower (starting ~15-30 minutes). Blood-brain barrier (BBB) status is a huge factor. If the BBB is not intact, as is often the case in CNS infections, mannitol can accumulate in brain tissue and actually draw fluid IN rather than OUT, possibly INCREASING ICP. It’s also worth talking about CPP. While both mannitol and 3% saline raise CPP (a good thing), 3% saline did better. This difference may be related to osmotic diuresis and lower blood pressure after mannitol.
This study was interesting and impactful. Though the primary outcome was physiology-centric rather than patient-centric, it is nice to see that a patient-centered outcome (functional status measured with Pediatric Cerebral Performance Category Scale) was different between groups – favoring 3% saline.
In short, 3% saline is already the preferred agent in TBI-related increased ICP, and this study suggests it’s better in meningitis/encephalitis also.”
Dr. Michael Wolf
Director of Neurocritical Care
Monroe Carell Jr. Children’s Hospital at Vanderbilt University