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meningitis" /></a></div><div class="bkr_bib"><h1 id="_NBK604106_"><span itemprop="name">Evidence review for osmotic agents in bacterial meningitis</span></h1><div class="subtitle">Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management</div><p><b>Evidence review G2</b></p><p><i>NICE Guideline, No. 240</i></p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2024 Mar</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-5773-6</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2024.</div></div><div class="bkr_clear"></div></div><div id="niceng240er23.s1"><h2 id="_niceng240er23_s1_">Osmotic agents for bacterial meningitis</h2><div id="niceng240er23.s1.1"><h3>Review question</h3><p>What is the effectiveness of osmotic agents in bacterial meningitis?</p><div id="niceng240er23.s1.1.1"><h4>Introduction</h4><p>Bacterial meningitis is a rare but serious infection, which can occur in any age group. Raised intracranial pressure is known to complicate bacterial meningitis and may impair cerebral perfusion or cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control raised intracranial pressure.</p><p>The aim of this review is to determine the effectiveness of using osmotic agents in bacterial meningitis.</p></div><div id="niceng240er23.s1.1.2"><h4>Summary of the protocol</h4><p>See <a href="/books/NBK604106/table/niceng240er23.tab1/?report=objectonly" target="object" rid-ob="figobniceng240er23tab1">Table 1</a> for a summary of the Population, Intervention, Comparison and Outcome (PICO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng240er23tab1"><a href="/books/NBK604106/table/niceng240er23.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img" rid-ob="figobniceng240er23tab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng240er23.tab1"><a href="/books/NBK604106/table/niceng240er23.tab1/?report=objectonly" target="object" rid-ob="figobniceng240er23tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">Summary of the protocol (PICO table). </p></div></div><p>For further details see the review protocol in <a href="#niceng240er23.appa">appendix A</a>.</p></div><div id="niceng240er23.s1.1.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng240er23.appa">appendix A</a> and the <a href="/books/NBK604106/bin/NG240-Methods-pdf.pdf">methods</a> document (supplementary document 1).</p><p>Declarations of interest were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng240er23.s1.1.4"><h4>Effectiveness evidence</h4><div id="niceng240er23.s1.1.4.1"><h5>Included studies</h5><p>Four randomised controlled trials were included in this review (<a class="bibr" href="#niceng240er23.ref1" rid="niceng240er23.ref1">Kilpi 1995</a>, <a class="bibr" href="#niceng240er23.ref2" rid="niceng240er23.ref2">Molyneux 2014</a>, <a class="bibr" href="#niceng240er23.ref3" rid="niceng240er23.ref3">Peltola 2007</a>, <a class="bibr" href="#niceng240er23.ref4" rid="niceng240er23.ref4">Sankar 2007</a>).</p><p>The included studies are summarised in <a href="/books/NBK604106/table/niceng240er23.tab2/?report=objectonly" target="object" rid-ob="figobniceng240er23tab2">Table 2</a>.</p><p>Three studies compared oral glycerol to placebo (<a class="bibr" href="#niceng240er23.ref2" rid="niceng240er23.ref2">Molyneux 2014</a>, <a class="bibr" href="#niceng240er23.ref3" rid="niceng240er23.ref3">Peltola 2007</a>, <a class="bibr" href="#niceng240er23.ref4" rid="niceng240er23.ref4">Sankar 2007</a>) and 1 study compared oral glycerol to no intervention for raised intracranial pressure (<a class="bibr" href="#niceng240er23.ref1" rid="niceng240er23.ref1">Kilpi 1995</a>). All studies were conducted in babies and children.</p><p>See the literature search strategy in <a href="#niceng240er23.appb">appendix B</a> and study selection flow chart in <a href="#niceng240er23.appc">appendix C</a>.</p></div><div id="niceng240er23.s1.1.4.2"><h5>Excluded studies</h5><p>Studies not included in this review are listed, and reasons for their exclusion are provided in <a href="#niceng240er23.appj">appendix J</a>.</p></div></div><div id="niceng240er23.s1.1.5"><h4>Summary of included studies</h4><p>Summaries of the studies that were included in this review are presented in <a href="/books/NBK604106/table/niceng240er23.tab2/?report=objectonly" target="object" rid-ob="figobniceng240er23tab2">Table 2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng240er23tab2"><a href="/books/NBK604106/table/niceng240er23.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img" rid-ob="figobniceng240er23tab2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng240er23.tab2"><a href="/books/NBK604106/table/niceng240er23.tab2/?report=objectonly" target="object" rid-ob="figobniceng240er23tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. </p></div></div><p>See the full evidence tables in <a href="#niceng240er23.appd">appendix D</a> and the forest plots in <a href="#niceng240er23.appe">appendix E</a>.</p></div><div id="niceng240er23.s1.1.6"><h4>Summary of the evidence</h4><p>This section is a narrative summary of the findings of the review, as presented in the GRADE tables in <a href="#niceng240er23.appf">appendix F</a>. For details of the committee’s confidence in the evidence and how this affected recommendations, see The committee’s discussion and interpretation of the evidence.</p><p>The evidence was assessed as being moderate to very low quality due to risk of bias (arising from selective reporting, missing outcome data and the randomisation process), imprecision (due to low event rates), and the inclusion of indirect populations and outcomes. See the GRADE tables in <a href="#niceng240er23.appf">appendix F</a> for the certainty of the evidence for each individual outcome.</p><p>The evidence showed no important differences between oral glycerol and placebo for allcause mortality or any long-term neurological impairment in babies and children. There was also no important difference between oral glycerol and no treatment for all-cause mortality, although a lower rate of any long-term neurological impairment was associated with oral glycerol relative to no treatment for raised intracranial pressure.</p><p>No eligible studies were identified that reported on other osmotic therapies or other outcomes defined in the protocol.</p><p>See <a href="#niceng240er23.appf">appendix F</a> for full GRADE tables.</p></div><div id="niceng240er23.s1.1.7"><h4>Economic evidence</h4><div id="niceng240er23.s1.1.7.1"><h5>Included studies</h5><p>A single economic search was undertaken for all topics included in the scope of this guideline, but no economic studies were identified which were applicable to this review question.</p></div></div><div id="niceng240er23.s1.1.8"><h4>Economic model</h4><p>No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation. This was because intervention is not expensive, and the committee did not expect their recommendations would change current NHS practice.</p></div><div id="niceng240er23.s1.1.9"><h4>The committee’s discussion and interpretation of the evidence</h4><div id="niceng240er23.s1.1.9.1"><h5>The outcomes that matter most</h5><p>Bacterial meningitis is associated with inflammation and swelling of the brain and high rates of mortality and morbidity. The aim of osmotic agents is to reduce brain swelling, and therefore pressure and distortion that may cause secondary brain injury. Therefore, all-cause mortality and brain herniation were chosen as critical outcomes due to the severity of these outcomes and the potential for osmotic agents to reduce intracranial pressure. Brain herniation was prioritised over reduction in intracranial pressure as is a more direct measure of the effectiveness of the intervention. Serious intervention-related adverse effects was also prioritised as a critical outcome due to concern about the potential for rebound raised intracranial pressure and the safety of osmotic agents.</p><p>In addition to reduction in intracranial pressure, long-term neurological impairment and functional impairment were selected as important outcomes as these are relatively common after bacterial meningitis and may be related to inflammation and swelling of the brain. Severe developmental delay was also included as an important outcome for children as this may be more commonly reported than neurological and functional impairment in this population.</p></div><div id="niceng240er23.s1.1.9.2"><h5>The quality of the evidence</h5><p>The quality of the evidence was assessed using GRADE methodology. The evidence was rated as moderate to very low quality, and reasons for downgrading the evidence included risk of bias (arising from selective reporting, missing outcome data and the randomisation process), imprecision (due to low event rates), and the inclusion of indirect populations and outcomes.</p><p>No evidence was found that reported brain herniation, serious intervention-related adverse effects, reduction in intracranial pressure, functional impairment, or severe developmental delay. There was no evidence identified for other osmotic therapies defined in the protocol (IV hypertonic saline and IV mannitol), or head-to-head comparisons between the osmotic therapies or IV Isotonic fluid.</p></div><div id="niceng240er23.s1.1.9.3"><h5>Benefits and harms</h5><p>The committee considered the evidence comparing oral glycerol to placebo or no treatment in babies and children with bacterial meningitis. The evidence showed no important differences between oral glycerol and placebo for all-cause mortality or any long-term neurological impairment, and no important difference between oral glycerol and no treatment for all-cause mortality. There was some evidence for a lower rate of any long-term neurological impairment associated with oral glycerol relative to no treatment for raised intracranial pressure. However, the committee noted that this finding was at odds to the placebo comparison, and this evidence was from a single study with an indirect population (included those with suspected as well as confirmed meningitis).</p><p>The committee considered this evidence alongside additional evidence that they were aware of, which is outlined in the ‘other factors the committee took into account’ section below. The committee agreed, based on their experience, that osmotic agents have only a transient effect on intracranial pressure. They are used to avert impending brain herniation and secondary brain injury while other measures with a more durable effect on intracranial pressure (such as intubation and ventilation or decompressive craniectomy) are considered and implemented, or until the underlying condition improves. In bacterial meningitis, definitive treatments for raised intracranial pressure are limited, and the disease process generally outlasts the effect of osmotic agents. Therefore, based on the evidence that it is unclear if glycerol reduces long-term neurological impairment, it may be associated with harm (see other factors the committee took into account), and the limited clinical rationale, the committee recommended that oral glycerol should not be used in the management of bacterial meningitis. The committee also recommended to avoid using other osmotic agents such as mannitol or hypertonic sodium chloride as part of routine management of bacterial meningitis due to an absence of evidence in these areas.</p><p>Based on their clinical knowledge and experience, the committee agreed that if there were signs of brain herniation, such as rapid change in level of consciousness, bradycardia, hypertension, or loss of pupillary reaction, it may be appropriate to use osmotic agents in the short-term to provide temporary control of intracranial pressure while other options are considered. Therefore, they recommended that osmotic agents (other than glycerol) could be considered if there are signs of brain herniation as they did not want to preclude this as an option, but they recommended that urgent advice should be sought from critical care clinicians for adults and from paediatric intensive care for babies and children.</p></div><div id="niceng240er23.s1.1.9.4"><h5>Cost effectiveness and resource use</h5><p>This review question was not prioritised for economic analysis and therefore the committee made a qualitative assessment of the likely cost-effectiveness of their recommendations. The committee did not recommend the use of osmotic agents as part of the routine management of bacterial meningitis. They recommended that they could be considered in the context of raised intracranial pressure when there are signs of brain herniation where they reasoned that an inexpensive intervention to mitigate catastrophic consequences of brain injury would be cost-effective. They noted that their recommendations reinforce current practice and would not have a significant resource impact.</p></div><div id="niceng240er23.s1.1.9.5"><h5>Other factors the committee took into account</h5><p>The committee were aware of an RCT (<a class="bibr" href="#niceng240er23.ref5" rid="niceng240er23.ref5">Ajdukiewicz 2011</a>) conducted in adults that was stopped early due to a higher rate of mortality in those receiving oral glycerol compared with those receiving placebo. This study was excluded from the current review as 83% of the population had immunodeficiency due to HIV. However, the committee agreed that the rationale for excluding people with HIV from the current guideline is related to differences in aetiology, rather than an impact of HIV on response to treatment. As this paper excluded people with cryptococcal or lymphocytic meningitis and the most common cause of bacterial meningitis was Streptococcus pneumoniae, the committee agreed that the study should be considered relevant to the population of interest for this guideline. Further, the committee were aware of further studies that showed that HIV was not associated with mortality (<a class="bibr" href="#niceng240er23.ref6" rid="niceng240er23.ref6">Wall 2013</a>, <a class="bibr" href="#niceng240er23.ref8" rid="niceng240er23.ref8">Wall 2017</a>) or white cell count (<a class="bibr" href="#niceng240er23.ref7" rid="niceng240er23.ref7">Wall 2014</a>) in people with bacterial meningitis. Therefore, the committee agreed that they could not exclude the possibility of harm associated with glycerol treatment in those without HIV.</p></div></div><div id="niceng240er23.s1.1.10"><h4>Recommendations supported by this evidence review</h4><p>This evidence review supports recommendations 1.9.3 to 1.9.5 in the NICE guideline.</p></div></div><div id="niceng240er23.rl.r1"><h3>References – included studies</h3><ul class="simple-list"><div id="niceng240er23.rl.r1.1"><h4>Effectiveness</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref1"><p id="p-120">
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<strong>Kilpi 1995</strong>
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</p>Kilpi, T., Peltola, H., Jauhiainen, T., Kallio, M. J.
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Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group, Pediatric Infectious Disease Journal, 14, 270–8, 1995 [<a href="https://pubmed.ncbi.nlm.nih.gov/7603807" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7603807</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref2"><p id="p-121">
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<strong>Molyneux 2014</strong>
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</p>Molyneux, E. M., Kawaza, K., Phiri, A., Chimalizeni, Y., Mankhambo, L., Schwalbe, E., Kataja, M., Pensulo, P., Chilton, L., Peltola, H.
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Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children. Pediatric Infectious Disease Journal, 33, 214–6, 2014
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[<a href="https://pubmed.ncbi.nlm.nih.gov/24136368" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24136368</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref3"><p id="p-122">
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<strong>Peltola 2007</strong>
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</p>Peltola, H., Roine, I., Fernandez, J., Zavala, I., Ayala, S.G., Mata, A.G., Arbo, A., Bologna, R., Mino, G., Goyo, J., Lopez, E., de Andrade, S.D.
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Sarna, S., Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Clinical Infectious Diseases, 45, 1277–1286, 2007
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[<a href="https://pubmed.ncbi.nlm.nih.gov/17968821" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17968821</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref4"><p id="p-123">
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<strong>Sankar 2007</strong>
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</p>Sankar, J., Singhi, P., Bansal, A., Ray, P., Singhi, S.
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Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis. Indian Pediatrics, 44, 649–656, 2007
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[<a href="https://pubmed.ncbi.nlm.nih.gov/17921553" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17921553</span></a>]</div></p></li></ul></div><div id="niceng240er23.rl.r1.2"><h4>Economic</h4><ul class="simple-list"><p>No studies were identified which were applicable to this review question.</p></ul></div><div id="niceng240er23.rl.r1.3"><h4>Other</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref5"><p id="p-125">
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<strong>Ajdukiewicz 2011</strong>
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</p>Ajdukiewicz, K. M., Cartwright, K. E., Scarborough, M., Mwambene, J. B., Goodson, P., Molyneux, M. E., Zijlstra, E. E., French, N., Whitty, C. J., Lalloo, D. G.
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Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial. The Lancet Infectious Diseases, 11, 293–300, 2011
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[<a href="/pmc/articles/PMC3999512/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3999512</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21334262" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21334262</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref6"><p id="p-126">
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<strong>Wall 2013</strong>
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</p>Wall, C. E., Catwright, K., Scarborough, M., Ajdukiewicz, K. M., Goodson, P., Mwambene, J., Zijlstra, E. E., Gordon, S. B., French, N., Fragher, B., Heyderman, R. S., Lalloo. D. G.
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High mortality amongst adolescents and adults with bacterial meningitis in Sub-Saharan Africa: an analysis of 715 cases from Malawi. PLoS ONE, 8, e69783, 2013
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[<a href="/pmc/articles/PMC3716691/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3716691</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23894538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23894538</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref7"><p id="p-127">
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<strong>Wall 2014</strong>
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</p>Wall, C. E., Everett, D. B., Mukaka, M., Bar-Zeev, N., Feasey, N., Jahn, A., Moore, M., van Oosterhout, J. J., Pensalo, P., Baguimira, K., Gordon, S. B., Molyneux, E. M., Carrol, E. D., French, N., Molyneux, M. E., Heyderman, R. S.
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Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000–2012. Clinical Infectious Diseases, 58, e137–45, 2014
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[<a href="/pmc/articles/PMC4001285/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4001285</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24496208" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24496208</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng240er23.ref8"><p id="p-128">
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<strong>Wall 2017</strong>
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</p>Wall, C. E., Mukaka, M., Scarborough, M., Ajdukiewicz, K. M. A., Cartwright, K. E., Nyirenda, M., Denis, B., Allain, T. J., Faragher, B., Lalloo, D. G., Heyderman, R. S.
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Prediction of outcome from adult bacterial meningitis in a high-HIV-seroprevalence, resource-poor setting using the Malawi Adult Meningitis Score (MAMS). Clinical Infectious Diseases, 64, 413–9, 2017
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[<a href="/pmc/articles/PMC5399948/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5399948</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27927860" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27927860</span></a>]</div></p></li></ul></div></ul></div></div><div id="appendixesappgroup1"><h2 id="_appendixesappgroup1_">Appendices</h2><div id="niceng240er23.appa"><h3>Appendix A. Review protocols</h3><p id="niceng240er23.appa.et1"><a href="/books/NBK604106/bin/niceng240er23-appa-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Review protocol for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 252K)</span></p></div><div id="niceng240er23.appb"><h3>Appendix B. Literature search strategies</h3><p id="niceng240er23.appb.et1"><a href="/books/NBK604106/bin/niceng240er23-appb-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Literature search strategies for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 198K)</span></p></div><div id="niceng240er23.appc"><h3>Appendix C. Effectiveness evidence study selection</h3><p id="niceng240er23.appc.et1"><a href="/books/NBK604106/bin/niceng240er23-appc-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Study selection for: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 157K)</span></p></div><div id="niceng240er23.appd"><h3>Appendix D. Evidence tables</h3><p id="niceng240er23.appd.et1"><a href="/books/NBK604106/bin/niceng240er23-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Evidence tables for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 201K)</span></p></div><div id="niceng240er23.appe"><h3>Appendix E. Forest plots</h3><p id="niceng240er23.appe.et1"><a href="/books/NBK604106/bin/niceng240er23-appe-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Forest plots for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 114K)</span></p></div><div id="niceng240er23.appf"><h3>Appendix F. GRADE tables</h3><p id="niceng240er23.appf.et1"><a href="/books/NBK604106/bin/niceng240er23-appf-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">GRADE tables for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 144K)</span></p></div><div id="niceng240er23.appg"><h3>Appendix G. Economic evidence study selection</h3><p id="niceng240er23.appg.et1"><a href="/books/NBK604106/bin/niceng240er23-appg-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Study selection for: What is the effectiveness of osmotic agents in bacterial meningitis?</a><span class="small"> (PDF, 95K)</span></p></div><div id="niceng240er23.apph"><h3>Appendix H. Economic evidence tables</h3><div id="niceng240er23.apph.s1"><h4>Economic evidence tables for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</h4><p>No evidence was identified which was applicable to this review question.</p></div></div><div id="niceng240er23.appi"><h3>Appendix I. Economic model</h3><div id="niceng240er23.appi.s1"><h4>Economic model for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</h4><p>No economic analysis was conducted for this review question.</p></div></div><div id="niceng240er23.appj"><h3>Appendix J. Excluded studies</h3><div id="niceng240er23.appj.s1"><h4>Excluded studies for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</h4><div id="niceng240er23.appj.s1.1"><h5>Excluded effectiveness studies</h5><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng240er23appjtab1"><a href="/books/NBK604106/table/niceng240er23.appj.tab1/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img" rid-ob="figobniceng240er23appjtab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng240er23.appj.tab1"><a href="/books/NBK604106/table/niceng240er23.appj.tab1/?report=objectonly" target="object" rid-ob="figobniceng240er23appjtab1">Table 7</a></h4><p class="float-caption no_bottom_margin">Excluded studies and reasons for their exclusion. </p></div></div></div><div id="niceng240er23.appj.s1.2"><h5>Excluded economic studies</h5><p>No studies were identified which were applicable to this review question.</p></div></div></div><div id="niceng240er23.appk"><h3>Appendix K. Research recommendations – full details</h3><div id="niceng240er23.appk.s1"><h4>Research recommendations for review question: What is the effectiveness of osmotic agents in bacterial meningitis?</h4><p>No research recommendation was made for this review.</p></div></div></div></div><div class="fm-sec"><div><p>FINAL</p></div><div><p>Evidence review underpinning recommendations 1.9.3 to 1.9.5 in the NICE guideline</p><p>This evidence review was developed by NICE</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2024.</div><div class="small"><span class="label">Bookshelf ID: NBK604106</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/38838181" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">38838181</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobniceng240er23tab1"><div id="niceng240er23.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Summary of the protocol (PICO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK604106/table/niceng240er23.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng240er23.tab1_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_niceng240er23.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_niceng240er23.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All adults, young people, children and babies (excluding neonates defined as aged 28 days old and younger) with confirmed bacterial meningitis.</td></tr><tr><th id="hd_b_niceng240er23.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_niceng240er23.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Osmotic therapy:
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<ul><li class="half_rhythm"><div>Orally administered glycerol</div></li><li class="half_rhythm"><div>IV hypertonic saline</div></li><li class="half_rhythm"><div>IV mannitol</div></li></ul>
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</td></tr><tr><th id="hd_b_niceng240er23.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_niceng240er23.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Head-to-head comparisons between the above osmotic therapies</div></li><li class="half_rhythm"><div>Isotonic fluid</div></li><li class="half_rhythm"><div>Placebo</div></li><li class="half_rhythm"><div>No intervention for raised ICP</div></li></ul>
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</td></tr><tr><th id="hd_b_niceng240er23.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</th><td headers="hd_b_niceng240er23.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><b>Critical</b></p><p>Population: adults, infants and children
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<ul><li class="half_rhythm"><div>All-cause mortality (measured up to 1 year after discharge)</div></li><li class="half_rhythm"><div>Brain herniation (may be reported as herniation, loss of pupillary reactivity, significant drop on Glasgow Come Scale, coning)</div></li><li class="half_rhythm"><div>Serious intervention-related adverse effects leading to death, disability or prolonged hospitalisation or that are life threatening or otherwise considered medically significant</div></li></ul></p>
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<p><b>Important</b></p>
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<p>Population: adults, infants and children
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<ul><li class="half_rhythm"><div>Reduction in intracranial pressure (measured either continuously or dichotomously based on study-defined cut-off)</div></li><li class="half_rhythm"><div>Any long-term neurological impairment (defined as any motor deficits, sensory deficits, cognitive deficits*, or behavioural deficits*; measured from discharge up to 1 year after discharge)</div></li><li class="half_rhythm"><div>Functional impairment (measured by any validated scale at any time point)</div></li></ul></p>
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<p>Population: infants and children
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<ul><li class="half_rhythm"><div>Severe developmental delay (defined as score of >2 SD below normal on validated assessment scales, or MDI or PDI <70 on Bayleys assessment scale, or inability to assign a score due to cerebral palsy or severity of cognitive delay; measured at the oldest age reported unless there is substantially more data available at a younger age)</div></li></ul></p>
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<p>*For infants and children below school-age, cognitive and behavioural deficits will be assessed at school-age.</p></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ICP: intracranial pressure; IV: intravenous; MDI: mental development index; PDI: psychomotor development index; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng240er23tab2"><div id="niceng240er23.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of included studies</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK604106/table/niceng240er23.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng240er23.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng240er23.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng240er23.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng240er23.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng240er23.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng240er23.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><th id="hd_h_niceng240er23.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_niceng240er23.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<a class="bibr" href="#niceng240er23.ref1" rid="niceng240er23.ref1">Kilpi 1995</a>
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</p>
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<p>RCT</p>
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<p>Finland</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=122</p>
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<p>Children 3 months to 15 years with suspected or confirmed bacterial meningitis</p>
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<p>Age in years (mean; SD): 3.5; 3.7</p>
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<p>Population treated with pre-admission antibiotics: 14%</p>
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<p>Case-fatality: 2%</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Oral glycerol (n=64)</u>
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</p>
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<p>4.5g/kg/day glycerol given orally/via nasogastric tube for 3 days</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>No intervention for raised ICP (n=58)</u>
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</p>
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<p>No further details reported</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>All-cause mortality</div></li><li class="half_rhythm"><div>Any long-term neurological impairment</div></li></ul>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Population is indirect as it included suspected and confirmed bacterial meningitis</p>
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<p>All children received ceftriaxone 100mg/kg/day IV for 4 days, followed by IM for 3 days. Those receiving dexamethasone received 1.5mg/kg/day IV</p>
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</td></tr><tr><td headers="hd_h_niceng240er23.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<a class="bibr" href="#niceng240er23.ref2" rid="niceng240er23.ref2">Molyneux 2014</a>
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</p>
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<p>RCT</p>
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<p>Malawi</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=360</p>
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<p>Children ≥2 months with confirmed bacterial meningitis</p>
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<p>Age: NR</p>
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<p>Population treated with pre-admission antibiotics: 46%</p>
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<p>Case-fatality: 26%</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Oral glycerol (n=182)</u>
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</p>
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<p>6g/kg/day 85% glycerol given orally/via nasogastric tube</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Placebo (n=178)</u>
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</p>
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<p>6ml/kg/day carboxymethylcellulose placebo</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>All-cause mortality</div></li><li class="half_rhythm"><div>Composite outcome: Any long-term neurological impairment, developmental delay or seizures</div></li></ul>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Population is indirect as 36% were HIV+</p>
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<p>All children received 100mg/kg/day IV ceftriaxone for 5 days. Those receiving paracetamol received 20mg/kg/6h suppository for 42 hours</p>
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</td></tr><tr><td headers="hd_h_niceng240er23.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<a class="bibr" href="#niceng240er23.ref3" rid="niceng240er23.ref3">Peltola 2007</a>
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</p>
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<p>RCT</p>
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<p>Argentina, Brazil, Dominican Republic, Ecuador, Paraguay and Venezuela</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=654</p>
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<p>Children 2 months to 16 years with confirmed bacterial meningitis</p>
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<p>Age in months (median; range): glycerol + dexamethasone: 12 (2 – 184); glycerol + placebo: 10 (2-152); placebo + dexamethaso ne: 13 (2-178); placebo + placebo: 10 (2-168)</p>
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<p>Population treated with antibiotics before diagnosis (unclear if pre-admission): 214/589 (36%)</p>
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<p>Case-fatality: 13%</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Oral glycerol (n=325)</u>
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</p>
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<p>1.5g/kg/6h 85% glycerol given orally/via nasogastric tube</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Placebo (n=329)</u>
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</p>
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<p>Oral placebo. No further details reported</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>All-cause mortality</div></li><li class="half_rhythm"><div>Any long-term neurological impairment</div></li></ul>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All children received 80-100mg/kg/day IV ceftriaxone for 7 - 10 days. Those receiving dexamethasone received 0.15mg/kg/6h IV</td></tr><tr><td headers="hd_h_niceng240er23.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<a class="bibr" href="#niceng240er23.ref4" rid="niceng240er23.ref4">Sankar 2007</a>
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</p>
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<p>RCT</p>
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<p>India</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=58</p>
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<p>Children 2 months to 12 years with confirmed bacterial meningitis</p>
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<p>Age in months (mean; SD): 50; 41</p>
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<p>Population treated with pre-admission antibiotics: 40%</p>
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<p>Case-fatality: 5%</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Oral glycerol (n=33)</u>
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</p>
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<p>1.5g/kg/6h glycerol given orally/via nasogastric tube</p>
|
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Placebo (n=25)</u>
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</p>
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<p>2% carboxymethylcellulose solution given orally/via nasogastric tube</p>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>All-cause mortality</div></li><li class="half_rhythm"><div>Any long-term neurological impairment</div></li></ul>
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</td><td headers="hd_h_niceng240er23.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All children received 100mg/kg/day IV ceftriaxone for minimum of 7 days. Those receiving dexamethasone received 0.15mg/kg/6h IV</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">HIV+: human immunodeficiency virus positive; ICP: intracranial pressure; IM: intramuscular; IV: intravenous; NR: not reported: RCT: randomised controlled trial; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng240er23appjtab1"><div id="niceng240er23.appj.tab1" class="table"><h3><span class="label">Table 7</span><span class="title">Excluded studies and reasons for their exclusion</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK604106/table/niceng240er23.appj.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng240er23.appj.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reason for Exclusion</th></tr></thead><tbody><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Ajdukiewicz, K. M., Cartwright, K. E., Scarborough, M., Mwambene, J. B., Goodson, P., Molyneux, M. E., Zijlstra, E. E., French, N., Whitty, C. J., Lalloo, D. G., Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial, The Lancet Infectious DiseasesLancet Infect Dis, 11, 293–300, 2011 [<a href="/pmc/articles/PMC3999512/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3999512</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21334262" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21334262</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population not of interest for review: 83% had immunodeficiency due to HIV</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Bhat, Smitha, How does glycerol compare with placebo for people with acute bacterial meningitis treated with antibiotics?, Cochrane Clinical Answers, 2018
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Summary of Cochrane review (Wall 2018)</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Glimaker, M., Johansson, B., Halldorsdottir, H., Wanecek, M., Elmi-Terander, A., Ghatan, P. H., Lindquist, L., Bellander, B. M., Neuro-intensive treatment targeting intracranial hypertension improves outcome in severe bacterial meningitis: an intervention-control study, Plos one, 9, 2014 [<a href="/pmc/articles/PMC3965390/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3965390</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24667767" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24667767</span></a>]
|
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention not of interest for review: intracranial pressure-targeted treatment (treatment based on ICP monitoring)</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Gwer, S., Gatakaa, H., Mwai, L., Idro, R., Newton, C. R., The Role for Osmotic Agents in Children with Acute Encephalopathies: A Systematic Review, JBI Library of Systematic ReviewisJBI Libr Syst Rev, 7, 154–174, 2009 [<a href="https://pubmed.ncbi.nlm.nih.gov/27820068" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27820068</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review updated by Gwer 2010</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Gwer, S., Gatakaa, H., Mwai, L., Idro, R., Newton, C. R., The role for osmotic agents in children with acute encephalopathies: a systematic review, BMC PediatricsBMC Pediatr, 10, 23, 2010 [<a href="/pmc/articles/PMC2859077/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2859077</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20398408" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20398408</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Includes populations not of interest for review: cerebral malaria, traumatic injury, cerebral oedema (not due to meningitis)</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Kumar, R., Singhi, S., Singhi, P., Jayashree, M., Bansal, A., Bhatti, A., Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children, Critical Care Medicine, 42, 1775–1787, 2014
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[<a href="https://pubmed.ncbi.nlm.nih.gov/24690571" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24690571</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population not of interest for review: only 30% had diagnosis of bacterial meningitis (remaining diagnoses: aseptic meningitis, fungal meningitis and viral encephalitis)</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Peltola, H., Roine, I., Improving the outcomes in children with bacterial meningitis, Current Opinion in Infectious DiseasesCurr Opin Infect Dis, 22, 250–5, 2009 [<a href="https://pubmed.ncbi.nlm.nih.gov/19369866" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19369866</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design not of interest for review: narrative review</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Peltola, H., Roine, I., Fernandez, J., Gonzalez Mata, A., Zavala, I., Gonzalez Ayala, S., Arbo, A., Bologna, R., Goyo, J., Lopez, E., Mino, G., Dourado de Andrade, S., Sarna, S., Jauhiainen, T., Hearing impairment in childhood bacterial meningitis is little relieved by dexamethasone or glycerol, PediatricsPediatrics, 125, e1–8, 2010 [<a href="https://pubmed.ncbi.nlm.nih.gov/20008417" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20008417</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes and analysis not of interest for review: secondary analysis of Peltola 2007 examining the effect of interventions and presenting status on different thresholds of hearing loss</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Shetty, R., Singhi, S., Singhi, P., Jayashree, M., Cerebral perfusion pressure-targeted approach in children with central nervous system infections and raised intracranial pressure: is it feasible?, Journal of Child Neurology, 23, 192–8, 2008
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[<a href="https://pubmed.ncbi.nlm.nih.gov/18263756" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18263756</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design and country combination not of interest for review: cohort study conducted in India</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Singhi, S., Jarvinen, A., Peltola, H., Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis, Pediatric Infectious Disease JournalPediatr Infect Dis J, 27, 892–6, 2008 [<a href="https://pubmed.ncbi.nlm.nih.gov/18776819" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18776819</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes not of interest for review: comparative outcome data only available for plasma osmolality and urine output</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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van de Beek, D., Brouwer, M. C., Randomised controlled trial: Hearing loss after bacterial meningitis is predicted by presenting status and young age; effectiveness of adjuvant dexamethasone or glycerol unclear, Evidence Based MedicineEvid Based Med, 15, 39–40, 2010 [<a href="https://pubmed.ncbi.nlm.nih.gov/20436113" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20436113</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design not of interest for review: commentary</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Vaziri, S., Mansouri, F., Sayad, B., Ghadiri, K., Torkashvand, E., Rezaei, M., Najafi, F., Azizi, M., Meta-analysis of studies comparing adjuvant dexamethasone to glycerol to improve clinical outcome of bacterial meningitis, Journal of Research in Medical SciencesJ, 21, 22, 2016 [<a href="/pmc/articles/PMC5122109/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5122109</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27904568" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27904568</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison not of interest for review: Dexamethasone versus glycerol</td></tr><tr><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Wall, E. C. B., Ajdukiewicz, K. M. B., Bergman, H., Heyderman, R. S., Garner, P., Osmotic therapies added to antibiotics for acute bacterial meningitis, Cochrane Database of Systematic Reviews, 2018 [<a href="/pmc/articles/PMC5815491/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5815491</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29405037" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29405037</span></a>]
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</td><td headers="hd_h_niceng240er23.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Includes populations not of interest for review: immunodeficiency due to HIV</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">HIV: human immunodeficiency virus; ICP: intracranial pressure</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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