# name
Modulació de la resposta inflamatòria sistèmica en nens críticament malalts després de la suplementació parenteral amb glutamina

# metadata.dc.contributor.other[].value
Universitat de Barcelona. Departament d'Àlgebra i Geometria

# metadata.dc.description.abstract[].value
En condicions d’estrès pot existir un dèficit relatiu de glutamina (Gln). Aquesta actua com a font energètica i en la protecció cel·lular, activant l’expressió de les “Heat Shock Proteins” (HSP). Disminucions en la seva concentració mitja provoquen una alteració en la regulació inflamatòria. La seva suplementació estimula mecanismes de mort bacteriana i disminueix l’explosió citotòxica. OBJECTIUS: Determinar la resposta inflamatòria en els pacients pediàtrics suplementats amb Gln parenteral respecte els que reben nutrició estàndard. Valorar la morbi-mortalitat. METODOLOGIA: Estudi prospectiu, a doble cec i aleatoritzat amb blocs balancejats. Es van recollir mostres analítiques i dades de la història clínica dels pacients ingressats en la Unitat de Cures Intensives Pediàtriques (UCIP) de l’Hospital Sant Joan de Déu de Barcelona. Criteris d’inclusió: pacients (1 mes – 14 anys), que van requerir nutrició parenteral (NPT), afectes d’infeccions sistèmiques o focals greus, i post operats cirurgia major abdominal. Criteris d’exclusió: pacients amb patologia prèvia de base i derivats d’altres centres amb evolució clínica de més de 48 h. Aleatorització en dos grups: Grup 1 o grup experimental al que es va administrar una solució d’aminoàcids (Aminopaed® o Vamin®) i es va suplementar amb Gln (Dipeptiven®), anomenat NPS + Gln. Grup 2 o grup control al que es va administrar una solució d’aminoàcids(Aminopaed® o Vamin®) no suplementada, anomenat NPS. Es van recollir 73 pacients en cada grup. Les variables a estudi van ser: edat; sexe; Pediatric Risk Score of Mortality II (PRISM-II) a l’ingrés; malaltia actual; nivells de limfòcits CD4, CD8 i CD4/CD8; valors d’interleuquines (IL) IL-6, IL-10 i de HSP-70 a les 0 hores (h) a les 48h al cinquè dia; i presència de sobre infecció, fallida multi orgànica i mortalitat. RESULTATS: Els nivells de Gln no van mostrar diferències entre els grups. El dia 5, els pacients del grup experimental presentaren nivells d’HSP-70 significativament superiors que el grup control (68,6 vs 5,4, p = 0,014). En tots dos grups, els nivells d’IL-6 van tenir un descens significatiu des de el dia 0 al dia (NPS: 42,24 vs 9,39, p < 0,001; NPS + Gln: 35,20 vs 13,80, p<0,001), però tan sols en el grup experimental va existir un descens significatiu entre el dia 2 i el dia 5 (13,80 vs 10,55, p = 0,013). Els nivells d’IL-10 no van variar durant les visites excepte en el grup control entre el dia 0 i el dia 2 (9,55 vs 5,356, p < 0,001). Al final de l’estudi no s’observaren diferències significatives entre els grups referent a l’estància en UCIP o a l’estància hospitalària, tot i que va haver una menor estada a intensius en els pacients suplementats amb Gln. No es van detectar efectes adversos en cap grup. CONCLUSIONS: La suplementació amb Gln en pacients crítics contribueix al manteniment de majors nivells d’HSP-70, durant més temps. Aquesta suplementació no influeix en els nivells d’IL-10 i no mostra disminució significativa dels nivells d’IL-6. La Gln podria disminuir la estada en la UCIP.

# metadata.dc.description.abstract[].value
[eng] In a stress situation, there is a Glutamine (Gln) deficit owing to an increase in its consumption as much as a decrease of its availability. This amino acid acts as a source of energy and also intervenes in the cellular and tissue protection activating the Heat Shock Proteins (HSP) expression. The Gln average concentration value is associated with a fall in immune response. It has been also proved that, if a supplement of Gln is added, it stimulates the mechanisms of bacteria death and diminishes the cytotoxic response. OBJECTIVES: To determine if there exist differences in the inflammatory response in seriously ill patients who received Gln supplemented nutrition with regard to those who received standard nutrition. To evaluate the patient clinical response and mortality. METHODOLOGY: It was a prospective, interventional, double blind, randomized and stratified clinical trial. Collection of samples and data for patients admitted at the Pediatric Intensive Care Unit (PICU) of the “Sant Joan de Déu” Hospital in Barcelona. Inclusion criteria: Patients (1 month to 14 years) who require parenteral nutrition, with one of the following diagnosis: Systemic or local infection and Major abdominal surgery. Exclusion criteria: patient with prior illnesses and patients coming from other centers with more than 48 hours clinical evolution. Sample selection: Group 1: Standard total parenteral nutrition (NPS) (Aminopaed® o Vamin®) and Gln perfusion (Dipeptiven®), denominated NPS + Gln. Group 2: Standard total parenteral nutrition (Aminopaed® o Vamin®) without Gln, denominated NPS. It will be necessary to include 73 experimental units in the reference group and 73 units in the experimental group. Variables: Age; sex; Pediatric Risk Score of Mortality (PRISM-II) score at admission; illness cause for the admission; CD4, CD8 i CD4/CD8 lymphocyte levels; determination at 0 hours (h), 48 h and 5th day of Interleukins(IL), IL-6, IL-10 and HSP-70; and infection complication, multiorganic failure and death. RESULTS: Gln levels failed to show statistical differences between groups. At day 5, patients in the experimental group had significantly higher levels of HSP-70 as compared with the control group (68.6 vs 5.4, p = 0.014). In both groups, IL-6 levels showed a remarkable descent from baseline and day 2 (SPN: 42.24 vs 9.39, p < 0.001; SPN + Gln: 35.20 vs 13.80, p<0.001) but only the treatment group showed a statistically significant decrease between day 2 and day 5 (13.80 vs 10.55, p = 0.013). Levels of IL-10 did not vary among visits except in the SPN between baseline and day 2 (9.55 vs 5.356, p < 0.001). At the end of the study, no significant differences between groups for PICU and hospital stay were observed. Although there was a shorter stay in the supplemented patients. No adverse events were detected in any group. CONCLUSIONS: Gln supplementation in critically-ill children contributed to maintain high HSP-70 levels for longer. Glutamine supplementation had no influence on IL-10 and failed to show a significant reduction of IL-6 levels. The Gln could reduce PICU stay.

# metadata.dc.format.extent[].value
In a stress situation, there is a Glutamine (Gln) deficit owing to an increase in its consumption as much as a decrease of its availability. This amino acid acts as a source of energy and also intervenes in the cellular and tissue protection activating the Heat Shock Proteins (HSP) expression. The Gln average concentration value is associated with a fall in immune response. It has been also proved that, if a supplement of Gln is added, it stimulates the mechanisms of bacteria death and diminishes the cytotoxic response. OBJECTIVES: To determine if there exist differences in the inflammatory response in seriously ill patients who received Gln supplemented nutrition with regard to those who received standard nutrition. To evaluate the patient clinical response and mortality. METHODOLOGY: It was a prospective, interventional, double blind, randomized and stratified clinical trial. Collection of samples and data for patients admitted at the Pediatric Intensive Care Unit (PICU) of the “Sant Joan de Déu” Hospital in Barcelona. Inclusion criteria: Patients (1 month to 14 years) who require parenteral nutrition, with one of the following diagnosis: Systemic or local infection and Major abdominal surgery. Exclusion criteria: patient with prior illnesses and patients coming from other centers with more than 48 hours clinical evolution. Sample selection: Group 1: Standard total parenteral nutrition (NPS) (Aminopaed® o Vamin®) and Gln perfusion (Dipeptiven®), denominated NPS + Gln. Group 2: Standard total parenteral nutrition (Aminopaed® o Vamin®) without Gln, denominated NPS. It will be necessary to include 73 experimental units in the reference group and 73 units in the experimental group. Variables: Age; sex; Pediatric Risk Score of Mortality (PRISM-II) score at admission; illness cause for the admission; CD4, CD8 i CD4/CD8 lymphocyte levels; determination at 0 hours (h), 48 h and 5th day of Interleukins(IL), IL-6, IL-10 and HSP-70; and infection complication, multiorganic failure and death. RESULTS: Gln levels failed to show statistical differences between groups. At day 5, patients in the experimental group had significantly higher levels of HSP-70 as compared with the control group (68.6 vs 5.4, p = 0.014). In both groups, IL-6 levels showed a remarkable descent from baseline and day 2 (SPN: 42.24 vs 9.39, p < 0.001; SPN + Gln: 35.20 vs 13.80, p<0.001) but only the treatment group showed a statistically significant decrease between day 2 and day 5 (13.80 vs 10.55, p = 0.013). Levels of IL-10 did not vary among visits except in the SPN between baseline and day 2 (9.55 vs 5.356, p < 0.001). At the end of the study, no significant differences between groups for PICU and hospital stay were observed. Although there was a shorter stay in the supplemented patients. No adverse events were detected in any group. CONCLUSIONS: Gln supplementation in critically-ill children contributed to maintain high HSP-70 levels for longer. Glutamine supplementation had no influence on IL-10 and failed to show a significant reduction of IL-6 levels. The Gln could reduce PICU stay.

# metadata.dc.source[].value
Tesis Doctorals - Departament - Obstetrícia i Ginecologia, Pediatria i Radiologia i Medicina Física

# metadata.dc.title[].value
Modulació de la resposta inflamatòria sistèmica en nens críticament malalts després de la suplementació parenteral amb glutamina