Changes in the sublingual microcirculation and endothelial adhesion molecules during the course of severe meningococcal disease treated in the paediatric intensive care unit

Paize, Fauzia; Sarginson, R. E.; Makwana, Nick; Baines, Paul; Thomson, A. P. J.; Sinha, Ian; Hart, C. A.; Riordan, Andrew; Hawkins, Kay; Carrol, Enitan D.; Parry, Christopher M.

doi:10.1007/s00134-012-2476-5

Cited by 40 publications

(35 citation statements)

References 32 publications

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“…However, of potential relevance to the present data is the observation that there is abnormal sublingual microcirculatory density and function in pediatric sepsis (25,26), which may be exacerbated by the microvascular sequestration of P. falciparum (27) in malaria. These factors might have attenuated the buccal absorption of ArTiMist in our children but may not have been influential in the upper small intestine.…”

Section: Discussionmentioning

confidence: 72%

“…There were 16 patients recruited to study 1 who received ArTiMist, but one was withdrawn after the second dose due to a protocol violation (incorrect drug storage). In study 2, a total of 76 patients were allocated to ArTiMist from the three sites (27,25, and 24 children from Rwanda, Ghana, and Burkina Faso, respectively). All patients responded to ArTiMist with prompt parasite clearance (median parasite clearance time in both studies, 24 h), and there were no treatment-related serious adverse events (data not shown).…”

Section: Patient Characteristicsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria

Salman

Bendel²,

Lee

et al. 2015

Antimicrob Agents Chemother

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A lthough parenteral artesunate is the recommended initial treatment for severe malaria (1), intramuscular (i.m.) artemether is an acceptable and practical alternative (1, 2). Artemether is also a recommended first-line oral therapy in combination with the longer half-life partner drug lumefantrine for uncomplicated Plasmodium falciparum (3) and Plasmodium vivax (4) infections. There are, however, few detailed studies assessing the pharmacokinetics of artemether and its active metabolite dihydroartemisinin (DHA) in either of these settings in children.Artemether-lumefantrine is a safe and effective treatment for uncomplicated pediatric malaria (3, 4), but there is evidence of significant between-dose variability in absorption even when coadministered with a small amount of fat to improve bioavailability (5). In addition, the nausea and vomiting that are frequently associated with malaria, together with an unwell child's refusal to feed or take medications by mouth (6), can reduce the effectiveness of oral treatment through reduced adherence to the World Health Organization (WHO) recommended 3-day regimen (7). In cases of more severe malaria, there is evidence of substantial between-patient variability in the absorption of i.m. artemether (8, 9), with some acidotic children likely exposed to subtherapeutic concentrations when the recommended doses are given (9). Rectal artesunate administration is associated with more rapid absorption and initial parasite clearance than is i.m. artemether administration in severely ill children (8). However, there is also marked between-patient variability in the dispositions of artesunate and DHA, and there is evidence that some children are able to expel artesunate suppositories even in the context of close monitoring as part of a formal pharmacokinetic evaluation (10). This might help explain why artesunate suppositories do not improve mortality compared to that with a placebo in older relative to younger pediatric age groups (11).There is a clear need for a prereferral formulation of an artemisinin derivative that can be easily administered and adequately absorbed in a child who may be unconscious or uncooperative or in whom nausea and vomiting preclude oral dosing. ArTiMist (Essential Nutrition Ltd., Brough, England) is an artemether formulation in neutral oil that can be administered as a metered sublingual spray and which is more rapidly and completely absorbed than is artemether given in tablet form in healthy adult volunteers (see accompanying paper [12]). In the present study, we assessed the pharmacokinetics of ArTiMist in African children with severe malaria or in whom gastrointestinal symptoms prevented the administration of artemether-lumefantrine tablets.

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Section: Discussionmentioning

confidence: 72%

Section: Patient Characteristicsmentioning

confidence: 99%

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria

Salman

Bendel²,

Lee

et al. 2015

Antimicrob Agents Chemother

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show abstract

“…The authors concluded that inadequate or suppressed shedding during sepsis might be associated with increased mortality, and they hypothesize that the shedding process is indeed protective for the host. Similarly, in a large pediatric ICU study on microcirculatory dysfunction in meningococcal sepsis in children, levels of sE-selectin, sVCAM-1 and sICAM-1,but not sP-selectin, were significantly increased in septic patients but negatively correlated with the degree of microcirculatory dysfunction (a measure of sepsis severity), as assessed by sublingual imaging [36].…”

Section: Soluble Adhesion Moleculesmentioning

confidence: 89%

Sepsis in Children

Mendez¹

2015

ETS

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“…There were negative correlations between the ICAM-1, VCAM-1, E-selectin levels and the microcirculatory values at the time of admission to PICU [19]. E-selectin, ICAM-1 and VCAM-1 were increased in both early and late pediatric sepsis [20], whereas meningococcal septic shock was associated with a significant and persistent increase in circulating soluble co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 concentration from 24-48 h up to day 7-8 following PICU admission [21].…”

mentioning

confidence: 88%