Pharmaconutrition in PICU. Gan Chin Seng Paediatric Intensivist UMMC

Transcription

1 Pharmaconutrition in PICU Gan Chin Seng Paediatric Intensivist UMMC

2 Pharmaconutrition in Critical Care Unit Gan Chin Seng Paediatric Intensivist UMMC

3 Definition New concept Treatment with specific nutrients to improve host defences and improve the outcome of critically ill patients E.g. glutamine, arginine, omega-3 fatty acids, selenium Less about energy requirements or nitrogen balance Pharmacological nutrition, Nutritional pharmacology

4 Background Critical illness causes systemic inflammation, altered immunity, & metabolic changes resulting in hypermetabolism Inability to maintain adequate nutrition leads to nutrient deficiencies, which may in turn increase the risk for infection, organ failure, & mortality

5 Artificial Nutrition Enteral (EN)/ parenteral (PN) ADJUNCTIVE support Debates on energy requirements & protein losses in past 40 years Early EN once haemodynamically stable within 3 days to avoid mucosal atrophy No immediate benefit with supplemented PN when intolerant to early EN in the absence of malnutrition ESPEN 2009: early ASPEN 2009: 7-10 days (Heidegger et al. Lancet. 2012; )

6 Immunonutrition Immune- enhancing diet (IED) Past 3 decades Enteral formulations or cocktails enrished in various nutrients Macronutrients: glutamine, arginine, omega-3 FAs Micronutrients: Vits A, C & E, selenium & zinc Various concentrations (special formula) To optimize immune function & cell recovery

7 Current evidence suggests that IED is beneficial in major elective surgery, trauma, burns, head and neck cancer, & non-septic critically ill patients on mechanical ventilation IED in severe sepsis/ critically ill patients is controversial (McClave SA et al. JPEN 2009;33: ) Mortality rate (Zaloga GP. Crit Care Med, 1998; 26:1143±1146) Canadian Clinical Practice Guidelines Committee recommended that IEDs should not be used in critically ill patients (Heyland DK. J Parenter Enteral Nutr 2003; 27: )

8 Over 30 RCTs of immunonutrition in over 2000 critically ill patients No benefit on outcome No evident to support (Kieft H et al. Intensive Care Med. 2005;31:524 32; Ochoa JB. Crit Care Med 2008;36:347 8) 597 patients, high-protein formula enriched with arginine, glutamine, antioxidants, & omega-3 FAs No change in outcome (Heyland et al. Crit Care Med. 2013; ) Poor methodological quality & small sample size Various nutrient combinations Heterogeneous patient population ( MIXED COCKTAIL approach)

9 Pharmaconutrition In 2008, Jones & Heyland proposed administration of specific nutrients in supranormal amounts has pharmacological effects on the inflammatory response to critical illness & can improve clinical outcomes ACTIVE therapeutic treatment (Jone and N.E. Heyland. Current Opinion in Gastroenterology. 2008;24: ) (Preiser et al. Critical Care. 2015; 19:35)

10 Meguid et al. (Ann Surg 2009) & Dupertuis et al. (Curr Opin Clin Nutr Metab Care 2009) suggested pharmaconutrition with disease-dedicated therapy approach Last decade Increasing evidences of therapeutic effects Impact on clinical outcomes NO Paediatric data (Meguid MM et al. Ann Surg 2009;249:364 5) (Dupertuis YM et al. Curr Opin Clin Nutr Metab Care 2009;12: )

11 Glutamine Non-essential amino acid Fuel for rapidly dividing cells e.g. lymphocytes, enterocytes, & colonocytes Protects structural & functional integrity of intestinal mucosa Augments cellular immune functions Precursor for endogenous synthesis of arginine Most extensively studied

12 Early small studies, benefits: antioxidant defenses, immune function, & N 2 retention Enhance tissue Heat Shock Protein (HSP) expression & reduce cellular apoptosis & cytokine release Improve tissue metabolic function Enhance stress tolerance Infectious complications (RR 0.79, 95% CI , P = 0.005) Mortality, especially with PN (RR 0.75, 95% CI , P = 0.008) Decreased length of hospital stay & ventilator time (Wischmeyer PE. Crit Care Med. 2007;35(suppl 9):S541 4) (Canadian clinical practice guidelines, ESPEN guideline on PN, SCCM & ASPEN 2009)

13 More recent studies, conflicting results In the Scottish Intensive Care Glutamine or Selenium Evaluative Trial No measurable improvement in new infection rates or survival (Andrews PJ et al. BMJ. 2011;342:d1542) Scandinavian glutamine trial Reduction in mortality when received glutamine for more than 3 days 3 meta-analysis: conflicting results (Wernerman J et al. Acta Anaesthesiol Scand. 2011;55:812 8) (Fadda V et al. Clin Nutr. 2013;32:492 3; Bollhalder L et al. Clin Nutr. 2013;32:213 23; Heyland D, et al. N Engl J Med. 2013;368: ) Very different approaches in dosing, timing, & backgrounds Used with caution, & harmful effects yet to be clarified

14 Arginine Metabolized by NO synthase to NO Stimulates release of hormones: GH, prolactin & insulin number & function of T cells Depletion of arginine & T-cell activation & immunocompetence, risk of infection With sepsis NO synthase upregulated, high arginine could be harmful Catabolic state, low serum arginine Dietary intake Uptake in endothelium, liver, and intestine Metabolism

15 Mortality & worsened shock In sepsis (Bertolini G. Intensive Care Med. 2003;29:834 40) Beneficial for elective surgery patients in reducing post-op infection (Drover JW. J Am Coll Surg. 2011;212:385 99)

16 Omega-3 Fatty Acid Fish oil, borate oil Incorporation into inflammatory cell membrane phosopholipids, leukotriene B 4,thromboxane A 2 & prostaglandin E 2 production Mixed report 60% mortality reduction ALI & ARDS (Pontes-Arruda A. J Parenter Enteral Nutr. 2008;32: ) (Zhu D et al. Intensive Care Med. 2014;40: )

17 2013 & 2015 Canadian Clinical Practice guideline ( Insufficient data to recommend use of fish oil alone for critically ill Lack of treatment effect on outcome Too sparse data

18 2008 meta-analysis of 3 studies demonstrated that enteral formula enriched with fish oils, borate oils & antioxidants significantly reduces mortality (RR 0.63, 95% CI 0.48, 0.84, P=0.002) in ARDS (

19 Canadian Clinical Practice guideline ( & 2015: enteral formula with fish oils, borage oils & antioxidants in ALI & ARDS should be considered Overall treatment effect on mortality decreased Lack good control group in several studies ( high fat formula, additional protein Lack of a treatment effect

20 Selenium & Antioxidants Part of a complex endogenous defence system protecting tissues from the damaging effects of oxidative stress Antioxidants, oxygen free radicals, systemic inflammatory response, subsequent cell injury, organ failure, & even higher mortality Selenium either alone or in combination with other trace elements & vits (Zn & vits A, C & E)

21 High-dose selenium (1000mcg/day) supplementation in 249 pts with severe systemic inflammatory response syndrome, sepsis, & septic shock demonstrated a large, but not significant, reduction in mortality [odds ratio (OR) 0.66, 95% CI 0.39, 1.10, P=0.109] Greater treatment effect detected in high normal levels of selenium compared with normal levels (Angstwurm MW et al. Crit Care Med 2007; 35: )

22 Mortality (RR 0.69, 95% CI 0.59, 0.82, P=0.0001), but had no effect on infectious complications or ICU length of stay in critically ill patients (Heyland DK et al. Intensive Care Med 2005; 31: )

23 High normal serum selenium was proposed as a target for result Antioxidant strategies, particularly selenium, should be considered for critically ill patients

24 Challenges Defining individual optimal dose Duration, efficacy, & routes of nutrient supplementation Heterogeneous patient populations

25 Summary Pharmaconutrition is an interesting field in critical area No Paediaric data yet Artificial nutrition/ immunonutrition/pharmaconutrition Glutamine/ arginine/ Omega-3 FAs (fish oil & borate oil)/selenium & antioxidants

26 Arginine: not recommended for sepsis Glutamine: needs further clarification Enteral fish oils, borage oils & antioxidants in ALI & ARDS should be considered High dose selenium could be helpful

27 THANK YOU