Evidence map›Paper›PMID 34223294›Full record

ArticleResuscitation plus

Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model.

Cindy H Hsu, Mohamad H Tiba, Brendan M McCracken, Carmen I Colmenero, Zachary Pickell, Danielle C Leander, Anne M Weitzel, Sarita Raghunayakula, Jinhui Liao, Tulasi Jinka and 6 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Resuscitation plus. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 38% of its field
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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Cindy H HsuDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Mohamad H TibaDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Brendan M McCrackenDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Carmen I ColmeneroDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Zachary PickellDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Danielle C LeanderDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Anne M WeitzelDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Sarita RaghunayakulaDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Jinhui LiaoDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Tulasi JinkaDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Brandon C CummingsDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Manjunath P PaiDepartment of Clinical Pharmacy, College of Pharmacy, University of Michigan Medical School, Ann Arbor, MI, USA.
Hasan B AlamMichigan Center for Integrative Research in Critical Care, University of Michigan Medical School, Ann Arbor, MI, USA.
Kevin R WardDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Thomas H SandersonDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Robert W NeumarDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
University of Michigan · US

Funding

Simple Automatic Perfusion System for salvage after cardiac arrestR44HL091606 · NHLBI · MC3, INC. · PI MAZUR, DANIEL EDWARD, NEUMAR, ROBERT W. · 2009 to 2018
$3.7M
ECPR After Prolonged Cardiac Arrest: Targeting Mechanisms of the No-ReflowR01HL133129 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARTLETT, ROBERT H., NEUMAR, ROBERT W. · 2017 to 2020
$3.1M
K12: Career Development in Emergency Critical Care ResearchK12HL133304 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NEUMAR, ROBERT W., PINSKY, DAVID J. · 2016 to 2020
$2.2M
Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest (EROCA) Trial Planning GrantR34HL130738 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARTLETT, ROBERT H., NEUMAR, ROBERT W. · 2016 to 2017
$698k
NHLBI NIH HHS K12 HL133304NHLBI NIH HHS R01 HL133129NHLBI NIH HHS R34 HL130738NHLBI NIH HHS R44 HL091606
6 · The paper itself

Abstract

aimHigh-dose valproic acid (VPA) improves the survival and neurologic outcomes after asphyxial cardiac arrest (CA) in rats. We characterized the pharmacokinetics, pharmacodynamics, and safety of high-dose VPA in a swine CA model to advance clinical translation.

methodsAfter 8 ​min of untreated ventricular fibrillation CA, 20 male Yorkshire swine were resuscitated until return of spontaneous circulation (ROSC). They were block randomized to receive placebo, 75 ​mg/kg, 150 ​mg/kg, or 300 ​mg/kg VPA as 90-min intravenous infusion (n ​= ​5/group) beginning at ROSC. Animals were monitored for 2 additional hours then euthanized. Experimental operators were blinded to treatments.

resultsThe mean(SD) total CA duration was 14.8(1.2) minutes. 300 ​mg/kg VPA animals required more adrenaline to maintain mean arterial pressure ≥80 ​mmHg and had worse lactic acidosis. There was a strong linear correlation between plasma free VPA C

conclusionsUp to 150 ​mg/kg VPA can be safely tolerated as 90-min intravenous infusion in a swine CA model. High-dose VPA induced dose-dependent increases in brain histone H3 and H4 acetylation, which can be predicted by plasma free VPA C

Indexed as

Cardiac arrestHistone acetylationPharmacodynamics biomarkerPharmacokineticSwine modelValproic acid

Identifiers

PMID34223294
PMCPMC8244526
OpenAlexW3033486395

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.