Timing of Parenteral Nutrition

Transcription

1 Timing of Parenteral Nutrition Arun Bansal; MD, FCCM, MRCPCH Professor Pediatric Critical Care PGIMER, Chandigarh, INDIA

2 Malnutrition in Critically Ill Incidence: from 19 32% Associated with increased morbidity and mortality Associated with an increase in risk- adjusted mortality as well as PICU length of stay Pollack M. Nutritional depletions in critically ill children: associations with physiologic instability and increased quantity of care. JPEN J Parenter Enteral Nutr 1985; 9: Mikhailov TA, et al. Early Enteral Nutrition Is Associated With Lower Mortality in Critically Ill Children. JPEN J Parenter Enteral Nutr 2014; 38: Hulst J, et al. Malnutrition in critically ill children: from admission to 6 months after discharge. Clin Nutr 2004;23:

3 Metabolic Response To Critical Illness Critically ill patients follow 1 of 3 clinical paths. First Acute insult leads to rapid organ dysfunction and death. Second Underlying insult is reversed, and homeostasis re-established Metabolic response shifts from catabolic to anabolic. Third Extension of the second except the catabolic response persists and leads to chronic critical illness manifesting as persistent inflammation, muscle wasting, immunosuppression with propensity for nosocomial infections, and persistent organ dysfunctions Rosenthal MD, Moore FA. Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): a new phenotype of multiple organ failure. J Adv Nutr Hum Metab 2015;1:e784.

4 Metabolic Response To Critical Illness Metabolic stress response activates numerous pathways, including neuroendocrine, immune/inflammatory, and GI. Within seconds to minutes Sympathetic nervous system activation increases adrenergic receptor activity and adrenal output of norepinephrine and epinephrine Within seconds to hours Neuroendocrine component turns on the sympathetic nervous systems and hypothalamic-pituitary axis Within hours Hypo-thalamic-pituitary axis increases anterior pituitary release of adrenocorticotropic hormone, TSH, FSH, LH, and GH

5 Metabolic Response To Critical Illness This leads to accelerated catabolism, insulin resistance, increased energy substrate use, increased energy expenditure, a cumulative calorie deficit, and proteolysis. In health, protein breakdown and synthesis are balanced. Preiser JC, et al. Metabolic response to the stress of critical illness. Br J Anaesth 2014;113:

6 Malnutrition due to Critical Illness Nutritional status of ICU patients deteriorates rapidly due to severe catabolism even when patients are well nourished Within 10 days patients may lose 10 25% of their body protein content, most pronounced in patients with MODS Puthucheary ZA, et al. Acute skeletal muscle wasting in critical illness. JAMA 2013; 310:

7 Nutritional Deficiency and outcome Caloric deficits of 4000 to 10,000 calories have been associated with more organ failure and increased hospital length of stay. Negative nitrogen balance has been associated with development of ICU- acquired weakness and chronic critical illness. Villet S, et al. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clin Nutr 2005;24: Batt J, et al. Intensive care unit-acquired weakness: clinical phenotypes and molecular mechanisms. Am J Respir Crit Care Med 2013;187:238 Benefits of adequate nutrition Decrease muscle and tissue oxidation, increase mitochondrial function and protein synthesis, maintain lean body mass and enhance mobility

8 Nutrition in Critically Ill-Awareness Role of nutrition in the outcome of patients with critical illness is being increasingly recognized. First pediatric critical care nutrition guidelines by ASPEN in 2009 Substantial increase in research and publications Impact of nutritional status and nutrient delivery during critical illness has been demonstrated on clinical outcomes such as mortality, infectious complications, and LOS

9 Goal of Nutrition Optimal Nutrition is a fundamental goal in the care of critically ill children Optimal timing and best way to achieve this goal remains controversial

10 EN or PN PN was the primary mode of nutrition few decades back It has obvious benefits as it does not need to be interrupted for procedures or rely on gut motility But, since last 2 decades EN is the initial source of nutrition EN may not be possible in all children Supplemental PN refers to adding PN to patients receiving insufficient calories through EN

11 Role And Timing Of PN PN is delivery of nutritional components and fluid through an IV route Even though EN remains the preferred route for nutrition delivery, there is still a role for PN in critically ill patients Clearly, in a patient deemed to be high nutritional risk and unable to use the gut, early PN is recommended McClave SA, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016;40:

12 Early EN Vs Early PN - Adults CALORIES trial 2400 critically ill patients 33 English ICUs EN or PN within 36 hours No significant differences in the primary outcome of 30-day mortality or secondary outcome of infectious complications Lack of benefit with early PN may suggest inflated estimates of benefit in previous smaller trials In adults with unplanned admissions, both early PN or EN can be safely administered. Harvey SE. Trial of the route of early nutritional support in critically ill adults. NEJM 2014;372:488 9.

13 Timing of PN in Adults 3 RCTs of supplemental PN 2 studies - spn had no benefit over hypocaloric EN alone. In the EPaNIC trial 4640 critically ill patients randomized to Early spn or late PN Late PN group was more likely to be discharged alive (hazard ratio for early PN, 1.06; 95% CI, ; P <.04) and Fewer ICU-acquired infections (22.8% vs 26.2%; P <.008) Limitations 80% of patients were not malnourished; 60% were cardiac surgery patients, and the late PN group received 20% IV dextrose, vitamins, and trace elements, limiting external generalizability Casaer MP, et al. Early versus late PN in critically ill adults. NEJM 2011;365: Doig GS, et al. Early PN in critically ill patients with short-term relative contraindications to EEN: a RCT. JAMA 2013;309: Heidegger CP, et al. Optimisation of energy provision with supplemental PN in critically ill patients: a RCT. Lancet 2013;381:

14 Four RCTs and two prospective observational studies remained One RCT found a higher percentage of alive discharge at day 8 in the LPN group (p = 0.007) but no differences in ICU and in-hospital mortality. None other found differences in ICU or in-hospital mortality Contradicting or divergent results on other secondary outcomes In adult critically ill patients, there are no clinically relevant benefits of EPN compared with LPN with respect to morbidity or mortality

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17 Multicenter RCT, 1440 critically ill children Whether withholding PN for 1 week is clinically superior to providing early PN? Two primary end points New infection acquired during the ICU stay Adjusted duration of ICU dependency Number of days in the ICU and as time to discharge alive from ICU.

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19 With increasing doses of aminoacids Likelihood of acquiring a new infection higher (HRs per 10% increase between , p 0 029), Likelihood of earlier weaning from ventilation lower (HRs , p 0 045) Likelihood of earlier PICU discharge lower (HRs , p 0 030) More glucose during first 3 days of PICU stay independently associated with fewer infections (HRs , p 0 036) More lipids independently associated with earlier PICU discharge (HRs , p days 4 7). Conclusion Early administration of aminoacids, but not glucose or lipids, could explain harm caused by early supplemental parenteral nutrition in critically ill children.

20 New Infections Weaning

21 Fewer patients acquired IFI in late-pn (77/2328 Vs. 112/2312; p = 0.008) After adjusting for risk factors, the odds to acquire an IFI and the likelihood of acquiring an IFI at any time were lower in late-pn (OR adj: 0.66, 95% CI , p = 0.009; HR adj 0.70, 95% CI , p = 0.02)

22 Mean direct medical costs for patients were 21% lower ( , p = 0.007) Late PN ( , IQR per patient) Early PN ( , IQR per patient) PN only contributed 2.1% to the total cost reduction Main cost driver was intensive care hospitalisation costs ( , p = 0.003)

23 Limitations of PEPaNIC Heterogeneity of the Patient Majority underwent elective surgery ( 38%) predominantly cardiac Emergency surgery Medical and cancer Lot of heterogeneity of the patient population Critically ill and emergency patients have a much more pronounced catabolic state than elective surgery patients This result in a very different caloric and protein requirements

24 Limitations of PEPaNIC Potential Center Effects At all 3 centers: Different protocols for initiation of PN in the EPN Different macronutrient and caloric targets Different approaches to determine energy requirements Considerable variability in blood glucose management Tight glycemic control in Leuven Rotterdam and particularly Edmonton more liberal

25 Limitations of PEPaNIC Indication for Starting spn Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) score Not been validated for critically ill children. In the EPN group, spn was started on the first day in all patients Regardless of indication, age, or tolerance for EN Usually, EN is established as a first line of nutritional therapy Duration of PICU stay was < 4 days in ~ 50% of patients Thus, many may not even have required spn. Use of PN without a clear need may be detrimental and might explain the worse outcome in the EarlyPN group. 75% of patients in LatePN group discharged from PICU by day 7 and never received any PN

26 Limitations of PEPaNIC Supply Relative to Needs Energy intakes were based primarily on estimates and equations. Only in a subset of patients in the Edmonton center, based on indirect calorimetry. Appr 45% were infants Energy and nutrient requirements different from older children Only Rotterdam center, parenteral energy and nutrient provision adhered to current guidelines Some patients may have been under- or overfed with spn, which may have contributed to the poor outcome in the EarlyPN group.

27 Limitations of PEPaNIC Possible Causes for Increased Infection PN may increase the risk of infection, especially in the reality of PICU settings with high staff workloads. Appr 40% of the PEPaNIC patients had infections at admission. High rate of pre-existing infections makes diagnosisng new infection difficult Bilirubin and CRP were significantly higher in the late PN group

28 Should PN be considered for patients at high nutrition risk when EN is not feasible? Yes, when EN is contraindicated or not feasible, PN should be considered as soon as possible (within 48 h) in high nutritional risk patients who are hemodynamically stable

29 Is it appropriate to consider supplemental PN? For patients with high nutritional risk, supplemental PN can be considered if EN fails to provide more than 60% of nutrition goal (calories and proteins) after 3 days. For all other patients, supplemental PN can be considered where EN fails to provide more than 60% of nutrition goal (calories and proteins) after 7 days

30 ESPEN Vs ASPEN ESPEN guidelines recommend the addition of SPN within 24 to 48 h in patients who are expected to be intolerant to EN within 72 h of admission ASPEN recommends postponing the initiation of PN until day 8 after ICU admission

31 Pediatric Guidelines Do not recommend initiation of PN within 24 hours of PICU admission. In children tolerating EN, stepwise advancement of nutrient delivery via the enteral route and delaying commencement of PN Mehta N, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. JPEN 2017; 41:

32 Summarize In children tolerating EN, stepwise advancement of nutrition Delay commencement of PN spn to reach a specific nutrient delievery goal is not known. Time to initiate spn is also unknown Threshold and timing of PN initiation should be individualized Based on a single RCT, spn should be delayed until 1 week in patients with normal baseline nutritional state and low risk of nutritional deterioration Based on expert consensus, PN supplementation in children who are unable to receive any EN during the first week In patients who are severely malnourished or at risk of nutritional deterioration, PN may be supplemented in the first week if they are unable to advance past low volumes of EN

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