Capillary leakage Hemodilution Pre-illness low TE status Diarrhea, Fistulas, Vomits High gastric volume Skin losses (burn patients, exudades) Drains.

Presentación del tema: "Capillary leakage Hemodilution Pre-illness low TE status Diarrhea, Fistulas, Vomits High gastric volume Skin losses (burn patients, exudades) Drains."— Transcripción de la presentación:

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3 Capillary leakage Hemodilution Pre-illness low TE status Diarrhea, Fistulas, Vomits High gastric volume Skin losses (burn patients, exudades) Drains (thorax, abdomen) Drugs (diuretics, corticosteroids) Low TE in enteral formulas and PN mixtures Hardy G, Hardy I, Manzanares W. Nutr Clin Pract 2012; 27:21-33.

4 Manzanares W, et al. Intensive Care Med 2009; 32:882-889. Group HVS Non SIRS SIRS SIRS-MODS Serum selenium (  g/L) p=.002 p=.0001

5 r 2 = 0.225; P= 0.003r 2 = 0.209; P= 0.005 Manzanares W, et al. Intensive Care Med 2009; 32:882-889. Serum selenium (  g/L (

6 5 10 15 20 25 30 35 40 APACHE II score Plasma Selenium (mM/L) 1.0 Forceville X, et al. Crit Care Med 1998; 26:1536-1544. Plasma Selenium (mM/L) 1.0 Sepsis Severe Sepsis Septic shock n= 15 (0) n= 13 (3) n= 12 (7) n= 134

7 A mayor severidad del insulto, Mayor depleción de AOX Reducción en los depósitos de AOX Reducción de los niveles intracelulares de Scavengers Reducción en la actividad enzimática

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9 ReferenceCombined therapyOutcomes Nathens et al Ann Surg 2002 Vit C 1000 mg IV q 8 h Vit E 1000 IU PO q 8 h  Organ Failure  ICU LOS Berger et al Crit Care 2006 Copper 2.5 to 3.1 mg/d, Selenium 315 to 380  g/d, and Zinc 26.2 to 31.4 mg/day for 8 to 21 days  Infections  Hospital Acquired Pneumonia (P < 0.001)  VAP (P= 0.023) Collier et al JPEN 2008 Vit C 1000 mg I.V q 8 h, α- Tocopherol 1,000 IU via naso- or orogastric tube q 8 h, and selenium 200 μg IV once daily Mortality (6.0 vs 8.6%, P =.001) 28% relative risk reduction in mortality  Hospital and ICU LOS No difference in ventilation days Berger et al Crit Care 2008 Selenium 270  g, Zinc 30 mg, Vit C 1.1 g, and vitamin B1 100 mg I.V  C-reactive protein Infectious complications and Hospital LOS did not differ Pontes Arruda et al Crit Care 2011 Borage/FO plus Vit E 320 IU/L, Vit C 820 mg/L, Vit A 12000 IU/L, B-carotene 670 mg/L Less severe sepsis and/or septic shock

10 A combination of antioxidant vitamins and trace minerals (specifically including selenium) should be provided to all critically ill patients receiving specialized nutrition therapy (Grade B) McClave SA, et al. JPEN 2009; 33: 277-316. Based on 7 level 1 and 16 level 2 studies, the use of supplemental combined vitamins and trace elements should be considered in critically ill patients. There are insufficient data to make a recommendation regarding IV/PN selenium supplementation. www.criticalcarenutrition.org

11 Glutamina 0.35 g/kg/d Selenio 500 μ g/d Parenteral Glutamina 30 g/d Vitamina C 1500 mg/d Vitamina E 500 mg/d β-Caroteno 10 mg/d Zinc 20 mg/d Selenio 300μg/d Enteral  Altas dosis son seguras y asociadas a:  Mayor resolución del estrés oxidativo  Preservación de los niveles de GSH  Mejoría de la función mitocondrial Heyland DK, et al. JPEN 2007.

12 Antioxidants vs. No Antioxidants (P= 0.87) Heyland DK, et al. NEJM 2013, in press.

13 * both survivors and non-survivors AntioxidantsNo Antioxidants P values Hospital LOS 16.9 (8.0 to 36.2) 16.6 (8.1 to 33.0) 0.97 ICU LOS 8.4 (4.6 to 15.3) 8.9 (5.1 to 15.8) 0.87 Infections All infections Urinary Tract Infections ICU Acquired Pneumonia 168 (27.2%) 39 (23.2%) 71 (42.3%) 181 (30.1%) 25 (13.8%) 95 (52.5%) 0.27 0.02 0.06 Days from randomization to final MV discontinuation * 6.0 (2.8 to 11.8) 6.1 (2.9 to 12.7) 0.69 Heyland DK, et al. NEJM 2013, in press.

14 AntioxidantNo AntioxidantP values* Days with shock Median [ Q1, Q3 ]3.0 [2.0, 6.0]3.0 [2.0, 5.0]0.58 Proportion of patients developed renal failure after enrollment (requiring dialysis) 46 (15.6%)36 (13.7%)0.53 Baseline SOFA score Mean ± SD (range)8.4±2.8 (0.0-15.0)8.5±2.8 (0.0-16.0)0.67 Maximal SOFA score Mean ± SD (range)11.1±2.9 (3.0-19.0)11.1±3.0 (0.0-19.0)0.82 Delta SOFA score Mean ± SD (range)2.7±2.6 (0.0-15.0)2.7±2.7 (0.0-14.0)0.29 Heyland DK, et al. NEJM 2013, in press.

15 I.El cóctel AOX fue seguro (no SAE) pero no mejoró ningún outcome clínico I.Asuencia de deficiencia de Selenio en los paciente con MOF II.Dosis insuficiente de Selenio III.Ausencia del Bolo IV inicial Heyland DK, et al. NEJM 2013, in press.

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17 Duntas LH. Horm Metab Res 2009; 41:443-447. P65P50 NF-  B TNF-  IL-1 IL-6 LIVER SELENOENZYMES CRP NUCLEUS BINDING TO PROMOTER CYTOPLASMA SELENIUM supplementation

18 Manzanares W  Hardy G. Curr Opin Clin Nutr Metab Care 2009;12: 273-80. Inhibición directa y reversible de la unón ADN-NF-  B Citotoxicidad de células proinflamatorias Efecto virucida y bactericida directo

19 Whang Z, et al. Shock 2009; 32:140-6. Plasma Selenium (µmol/L) Mejora la microcirculación Mejora la función miocárdica Reduce la mortalidad

20 Huang TS, et al. PLOS One 2013; 8:e54431. 0.73 (0.58, 0.94) P= 0.01 Dosis Carga I.V Disminuye la Mortalidad

21 Angstwurm MWA, et al. Crit Care Med 2007; 35:118-126. 50%39%56%42% P= 0.049 P= 0.109 n= 249, APACHE III  70 1000  g of Se as a 30-min i.v bolus, 14 daily continuous infusions of 1000  g i.v

22 Clinical Outcome Selenite Placebo P values  SOFA (day 0-10) 7.8±3.84.7±2.0 0.02 Early VAP, no. of episodes (%) 1 (6.7)6 (37.5%)0.04 Late VAP, no. of episodes (%) 2 (13.3)1 (6.3)0.68 Episodes of HAP after ICU discharge 030.03 Days of Antibiotics 8.8±5.39.5±2.3 0.19 Median time of Catecholamines therapy (d) 2.1 ± 1.44.0 ± 4.30.69 Manzanares W, et al. Intensive Care Med 2011;37:1120-1127. IV bolus 2.000  g Se over 2 h within 24 h after enrolment, and thereafter 1.600  g/d Se as a daily continuous infusion for 10 days

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24 Manzanares W, et al. Crit Care 2012; 16:R66. 55 relevant citations were identified, 1980-2011 N= 21 RCTs (2531 patients) met inclusion criteria n= 14 trials did not include ICU patients n= 7 trials studied nutrients other than micronutrients n= 4 trials did not evaluate relevant clinical outcomes n= 2 meta-analysis; n= 3 duplicated publications; n= 4 other reasons

25 0.82 (0.72-0.93) P= 0.002 Manzanares W, et al. Crit Care 2012; 16:R66.

26 Antioxidants significantly decrease ventilation days in ICU patients, P= 0.02 -0.67 (-1.22,-0.13) P= 0.02 Manzanares W, et al. Crit Care 2012; 16:R66.

27 0.79 (0.68-0.92) P= 0.003 Manzanares W, et al. Crit Care 2012; 16:R66.

28 I.Antioxidantes (vitaminas y elementos traza) pueden reducir la mortalidad y acortar los tiempos de ventilación mecánica II.El efecto terapéutico es mayor en los pacientes más graves III.El empleo de cócteles antioxidantes asociados a selenio intravenoso 500 μ g/d o una dosis mayor puede optimizar el efecto terapéutico de las estrategias antioxidantes Manzanares W, et al. Crit Care 2012; 16:R66.

29 Alhazzani, Jacobi, Sindi, Hartog, Reinhart, Kokkoris, Gerlach, Andrews, Debrak, Manzanares, Cook, Jaescke. Crit Care Med 2013. Monoterapia con Selenio I.V reduce la Mortalidad en la sepsis (0.73, 95% CI 0.54-0.98, P= 0.03) 0.73 (0.54-0.98) P= 0.03

30 Alhazzani W, et al. Crit Care Med 2013, in press. Manzanares W, et al. Crit Care 2012; 16:R66. Parenteral Selenium in ICU (Monotherapy) Mortality RR= 0.86, 95% CI 0.73,1.01 P= 0.0 6 (9 RCTs) High Dose > 500  g/L RR= 0.80, 95% CI 0.63,1.02 P= 0.0 7 (4 RCTs) Parenteral Selenium in Sepsis (Monotherapy) Mortality OR: 0.73, 95% CI 0.54,0.98 P= 0.034 (9 RCTs) High Dose > 500  g/L OR: 0.67, 95% CI 0.47,0.97 P= 0.03 (5 RCTs) Langlois PL, Hardy G, Manzanares W. Reanimation 2013 In press.

31 Mortalidad con la Suplementación de Selenio MORTALIDAD (9 RCTs) RR 0.83, (95% CI 0.70,0.99 P = 0.04, heterogeneity I 2 =0% TERAPIA ≥ 7 DÍAS (8 RCTs) RR 0.77, 95% CI 0.63,0.94, P= 0.01; heterogeneity I 2 = 0% DOSIS DIARIA ≥ 1000 μ g/d (4 RCTs) RR 0.77, 95% CI 0.61,0.99, P=0.04; heterogeneity I 2 = 0% Huang TS, et al. PLOS ONE 20138; e54431.

32 I. Fármaco-nutrición parenteral con Selenio (bolo + infusión i.v) parece ser una estrategia exitosa en la sepsis/sepsis grave II. Selenio parenteral se asocia a una reducción de la mortalidad III. Monoterapia I.V a altas dosis (> 500-1000  g/d) iniciada en las primeras 6 horas y al menos por 7 días es superior Manzanares W, Langlois P, Hardy G. Curr Opin Clin Nutr Metab Care 2013. In press

33 SELENIO Grado 2C Evidencia sobre Se i.v es aun muy débil Dosis óptima y Tiempo de administración SIN respuestas Bajas dosis de Selenio deben ser usadas en la NP Dellinger RP, et al. Crit Care Med 2013; 41:580.

34 Heyland et al, Intensive Care Med 2005 Manzanares et al, Crit Care 2012 Evidencia reciente fue omitida Estudio SERENITE (Forceville, 2007) (n= 60, infusión tardía, no dosis carga) 1 2 3 Manzanares W, Langlois P, Hardy G. Curr Opin Clin Nutr Metab Care 2013. In press

35 11.1 PN Selenium High Dose 11.2 PN Selenium Dose=500 Micrograms 11.3 PN Selenium Low Dose 0.88 (0.78-0.99) P= 0.04 www.criticalcarenutrition.comwww.criticalcarenutrition.com April 2013

36  The use IV/PN selenium supplementation, alone or in combination with other antioxidants, should be considered in critically ill patients  Since 2009, 6 new trials (El Attar 2009, Montoya 2009, Andrews 2011, Manzanares 2011, Valenta 2011 and Heyland 2013) showed a significant treatment effect of Selenium supplementation with respect to reduced infections

37 La evidencia actual sugiere que los Antioxidantes pueden reducir la Mortalidad en UCI La Farmaconutrición con Selenio mejora Selenium outcomes clínicos, en particular en la sepsis severa Selenio (Bolo i.v + infusión i.v) con una dosis diaria > 500-1000 μ g/día debería ser considerada en los pacientes críticos El estudio SISPCT puede sumar evidencia sobre los efectos e indicaciones del Selenio i.v en la sepsis severa Manzanares W & Hardy G. ICU Management, Winter 2013.

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