Evidence map›Paper›PMID 42230477›Full record

ArticleNeurocritical care2026

Adjunctive Mechanical Ventilation or Intravenous Hypertonic Saline in Malawian Children with Cerebral Malaria and Highly Increased Brain Volume: A Randomized, Phase 3 Clinical Trial.

Nicole F O'Brien, Douglas G Postels, Yamikani Chimalizeni, Yudy Fonseca, Gavin Wooldridge, Elizabeth Parker, Xochilt Galeano, Evangelina Urbina, Michael Lintner-Rivera, Hunter J Wynkoop and 18 more

Abstract read
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In one paragraph

Article in Neurocritical care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Nicole F O'BrienDivision of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA. Nicole.OBrien@nationwidechildrens.org.ORCID http://orcid.org/0000-0002-8826-8671
Douglas G PostelsDivision of Neurology, George Washington University/ Children's National Hospital, Washington, DC, USA.
Yamikani ChimalizeniDepartment of Paediatrics and Child Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
Yudy FonsecaDivision of Critical Care, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Gavin WooldridgePerth Children's Hospital, Perth, Australia.
Elizabeth ParkerDivision of Critical Care, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Xochilt GaleanoDivision of Pediatric Critical Care Medicine, Department of Pediatrics, Hospital Privado Salud Integral, Managua, Nicaragua.
Evangelina UrbinaDivision of Critical Care, Department of Pediatrics, Universidad Autónoma de Mexico, Mexico City, Mexico.
Michael Lintner-RiveraDivision of Critical Care, Department of Pediatrics, University of Indiana, Bloomington, USA.
Hunter J WynkoopDivision of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
Karen ChetcutiRadiology Division, Department of Paediatrics and Child Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
Manu S GoyalMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Eric Biondo-SavinDepartment of Radiology, Michigan Institute for Neurological Disorders, Farmington Hills, USA.
Sandeep JuvvadiTenet Diagnostics, Hyderabad, India.
Jennifer NicholasCincinnati Children's Hospital Medical Center, Department of Radiology, Cincinnati, OH, USA.
Lorenna VidalDivision of Neuroradiology, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Madiha RaeesDivision of Critical Care, Department of Anesthesiology and Critical Care, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Allan DoctorDivision of Critical Care, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Kenneth E RemySchool of Medicine, Washington University in St. Louis, St. Louis, MO., Department of Pediatrics, University Hospitals of Cleveland, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Adnan BhuttaDivision of Critical Care, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA.
Adrian HollowayDivision of Critical Care, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Christopher Alan MoxonCenter for Parasitology, School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Karl B SeydelDepartment of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
Alice M LiombaBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Cowles ChilinguloBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Khalid IbrahimCenter for Food Allergy and Asthma Research (CFAAR), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Joseph GardinerDepartment of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
Terrie E TaylorDepartment of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.

Funding

Division of Intramural Research, National Institute of Allergy and Infectious Diseases U01AI126610
6 · The paper itself

Abstract

backgroundCerebral malaria (CM) impacts hundreds of thousands of African children and causes significant morbidity and mortality. Beyond supportive care and antimalarials, treatments that improve outcomes have not been identified.

methodsWe conducted a randomized, open-label, phase 3 clinical trial in Blantyre, Malawi (2018-2023). Children aged 6 months to 12 years with CM (Blantyre Coma Score ≤ 2, Plasmodium falciparum parasitemia, and no alternative coma etiology) underwent magnetic resonance imaging (MRI) screening. Participants with severe brain swelling [brain volume score (BVS) 6-8] were randomized to early intubation and mechanical ventilation, 3% hypertonic saline (HTS), or usual care. The primary outcome was 7-day mortality. Secondary outcomes included neurologic morbidity in survivors, serious adverse events, and changes in transcranial Doppler (TCD)-measured cerebral blood flow velocities (CBFVs).

resultsOf 206 children screened with MRI, 57 met criteria for randomization (23 mechanical ventilation, 17 HTS, and 17 usual care). Neither mechanical ventilation nor HTS reduced 7-day mortality compared with usual care (risk difference - 0.075, 95% CI - 0.27 to 0.17, p = 0.59 for ventilation; 0.002, 95% CI - 0.22 to 0.28, p = 1.0 for HTS). Neurologic morbidity at hospital discharge did not differ between intervention groups and controls. HTS administration resulted in rapid and sustained increases in CBFVs in all major cerebral vessels. Among children with baseline cerebral hyperemia, those treated with HTS had significantly worse outcomes (combined neurologic morbidity or death) than hyperemic children receiving usual care (relative risk 3.0, 95% CI 1.02 to 10.9, p = 0.04).

conclusionsIn children with CM and severe brain swelling, adjunctive early mechanical ventilation or hypertonic saline does not improve survival or neurologic outcomes. Hypertonic saline increases cerebral blood flow and is associated with harm in children with baseline cerebral hyperemia. These findings demonstrate that non-phenotype-guided neuroprotective strategies are ineffective in CM and highlight the need for cerebrovascular endotype-informed therapeutic approaches.

Indexed as

Cerebral blood flowCerebral malariaHypertonic salineMechanical ventilation

Identifiers

PMID42230477

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.