1. Micronutrients in Critical care BY Ahmed Salah Lecturer of anesthesia &critical care

2. Micronutrients in the critically ill patient Nutritional support of the critically ill patient includes the daily provision of vitamins and trace elements. These compounds, collectively termed “micronutrients”, are essential not only as intermediaries in metabolism but also for their potential roles in cellular immunity, wound healing and antioxidant activity

3. Micronutrients in the critically ill patient  Any injured patient will develop an acute phase response (APR) and a systemic infammatory response syndrome (SIRS) with the production of various mediators, including cytokines, which modulate the metabolic response. SIRS is associated with a redistribution of vitamins and trace elements from the circulating compartment to tissues and organs, which are involved in protein synthesis and immune cell production.  The circulating concentrations of most trace elements (iron, selenium, zinc) and of their carrier proteins decrease as do the water-soluble vitamins, whereas copper and manganese increase,causing a relative defcit in circulating antioxidants.

4. Micronutrients in the critically ill patient Critical illness is associated with increased ROS production (and thus increased oxidative stress), and on the other hand low levels of most antioxidant micronutrients (endogenous antioxidant defenses).

5. Micronutrients in the critically ill patient Oxidative stress is defined as “a state in which the level of toxic reactive oxygen intermediates (ROI) /reactive oxygen species overcome the endogenous antioxidant defences of the host”

6. Micronutrients in the critically ill patient Free radicals cause a cascade of intracellular events resulting in the release of nuclear factor- kappa B (NF-Kb) in the cytoplasm, and subsequently enabling the initiation of the transcription process. NF- K B controls the production of acute phase mediators such as tumour necrosis factor (TNF-a), interleukin 2 (IL- 2), and IL-2 receptors, which in turn activate NF- K B, intensifying the infammatory cascade. In this regard, selenium has been shown to downregulate NF- K B,

7. Pathways leading to activation of NF-KB and the production of adhesion molecules. (Dinardo et a1,2008)

9. Vitamin A (retinol, carotene) Vitamin A is fat-soluble vitamin needed for the normal structure and functioning of the cells in the skin and body linings, e.g. in the lungs. This vitamin also helps with vision in dim light, as well a keeping the immune system healthy. It is found in two forms; retinol in foods from animal sources and carotenoids (the most abundant of which is the beta-carotene) from plant sources. Vitamin A – retinol is found in liver and whole milk, Vitamin A – carotenoids are found in dark green leafy vegetables, carrots and orange coloured fruits.

10. Vitamin E (Tocopherol) Vitamin E is a group of similar molecules with common properties and functions. Vitamin E acts as an antioxidant and protects cells in the body against damage. Vitamin E is mainly found in vegetable oils, nuts, seeds and wheat germ.

11. Thiamin (B 1 ) Thiamin is needed for the release of energy from carbohydrate. It is also involved in the normal functioning of the nervous system and the heart. Thiamin deficiency can lead to the development of the disease beri- beri. Symptoms include fatigue, weakness of the legs and anorexia.

12. Vitamin C (Ascorbic acid) Ascorbic acid is needed to make collagen which is required for the normal structure and function of body tissues, such as skin, cartilage and bones. It also acts as an antioxidant that protects the body from damage by free radicals. Sources of ascorbic acid include fresh fruits, especially citrus fruits and berries, green vegetables, peppers and tomatoes. Ascorbic acid is also found in potatoes (especially in new potatoes).

13. Anti-oxidants Vitamins A, C and E are anti-oxidants and work together in the body to protect cells against oxidative damage from free radicals. This damage to cells can increase the risk of developing diseases such as heart disease and cancer.

14. Selenium regulates free-radical scavenging systems low levels common in normals and ICU patients several small studies inconclusive but suggest benefit one large, flawed recent study showed non- significant mortality benefit

15. ZINC Beneficial effect of Zn in critical care: Repair of damaged tissues Protect the liver from endotoxin Co-factor function in acute phase protien synthesis and increased bacteriocidal capability after phagocytosis. Zn is thought to have benefial effect by decreasing microbial effect.

16. ZINC The decrease in serum Zn is related to redistribution of Zn to site of tissue injury. Surgical trauma increases corticosteroid secretion,which decreases s.Zn. Hypermetabolic trauma patient experience loss Zn through gastrointestinal tract,also loss throug urine may contribute

17. Micronutrient Deficiencies - I Essential Fatty Acids Scaly dermatitis Zinc Growth retardation Copper Anemia, Leukopenia ChromiumGlucose intolerance, Neuropathy Molybdenum Confusion, Cholestasis Selenium (Cardio)myopathy

18. Micronutrient Deficiencies - II Vitamin ANight blindness, keratosis Vitamin DOsteomalacia, Muscle weakness Vitamin ERetinal & posterior column nuclei dystrophy, Vitamin K Bleeding diathesis BiotinAlopecia, Dermatitis, Neuritis CarnitineAbnormal LFTs

19. Endogenous mechanisms work in a network-like fashion to neutralise the production of ROS in an attempt to counteract the deleterious effects thereof. Intracellular glutathione and nonenzymatic ROS scavengers (including vitamins such as ascorbic acid, β-carotene and a-tocopherol) form part of this highly evolved mechanism. Enzymatic systems [including superoxide dismutase (SOD), catalase and glutathione peroxidases (GSHPx)] then work synergistically to detoxify ROS further. These enzyme systems are dependant on minerals such as selenium, copper, zinc and manganese as important cofactors in these enzymatic reactions.

21. THEN WHAT TO DO?

22. EVIDENCE BASED RESULTS Mortality Fourteen of the 15 trials provided mortality data, When the results of all 14 RCTs were aggregated (n = 1468), overall, micronutrients were associated with a significant decrease in mortality (P = 0.0009) Six trials in total reported on 28-d mortality, and when the results of these trials were aggregated (n = 1194), micronutrient supplementation was associated with a significant decrease in 28-d mortality ( P = 0.0006)

23. EVIDENCE BASED RESULTS Infectious complications Although 11 of the 15 trials provided infectious complications data, trials indicated that micro­ nutrient supplements showed no significant effect on infectious complications ( P = 0.69). Length of hospital stay When the results of these four trials were pooled (n = 113), micro­nutrient supplementation was not associated with a significant difference in LOS, P = 0.75).

24. ENTERAL VS PARENTRAL ROUTE? This present review did not find clear evidence that parenteral is superior to enteral administration in terms of clinical outcomes,. The vast majority of trials available in the literature delivered micronutrients intravenously, with the intravenous route seen as the only reliable method by which micronutrients can be administered in the critically ill. Absorption by the enteral route in critically ill patients is unpredictable because of bowel edema, bowel ischemia, hemodynamic instability, fluid resuscitation, and alterations in blood supply. Conversely, delivering micro­nutrients to the gut may be beneficial through the prevention of the local gut inflammatory response, indicating that the two routes, in theory at least, do have advantages. Bearing in mind the important role of the gastrointestinal tract as a source of cytokine and leukocyte activation and ROS formation, the provision of key nutrients directly to the gastrointestinal tract makes biological sense. It is thus proposed that future studies investigate the use of parenteral and enteral administrations of micronutrients to maximize the opportunity of demonstrating a treatment effect, if one really exists.

25. WHEN TO GIVE? The timing of micronutrient supplementation is important and is probably a key factor because the repletion of micronutrients, and specifically of antioxidants, would probably achieve a greater efficacy if given before massive oxidative injury (e.g., severe sepsis or septic shock).

26. ARTICLES

27. CONCLUSION This show suggests potential benefit of micronutrient supplementation in critically ill adults by possibly being associated with a decrease in mortality but highlights that caution is warranted because nutrient interactions and risk of toxicity are not clearly defined in critical illness. Timing, duration, and dosing appear to be key factors to ensure optimal clinical benefit. Still larger studies with greater number of patients are warranated to determine a clear end of when,what and how nutrients are supplemented with other studies determining the optimum dosages.

28. Thank you