Journal Club - Early versus Late Parenteral Nutrition in Critically Ill Adults

3,751 views

Published on

Journal Club and article review presented at the Miami VA during my Pharmacy Surgery Elective Rotation.

Published in: Health & Medicine
0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
3,751
On SlideShare
0
From Embeds
0
Number of Embeds
5
Actions
Shares
0
Downloads
153
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide

Journal Club - Early versus Late Parenteral Nutrition in Critically Ill Adults

  1. 1. Early versus Late Parenteral Nutrition in Critically Ill Adults Joy A. Awoniyi, PharmD. Candidate Florida Agricultural and Mechanical University August 2, 2011 Surgery Elective Rotation Preceptor: Dr. Lisa Joseph N Engl J Med 2011 Authors: Casaer MP, Mesotten D, Hermans G, et. al.
  2. 2. Background • Parenteral Nutrition provides caloric requirements when other routes of administration are not possible • Short Bowel Syndrome • Bowel Obstruction • Chron’s Disease • Ulcerative Colitis • Starvation or underfeeding in intensive care unit patients is associated with increased morbidity and mortality • 20-40% of critically ill patients show evidence of protein- energy malnutrition • Optimal timing for the initiation of parenteral nutrition in critical care is a major area of uncertainty
  3. 3. Guideline Differences European Society of Enteral and Parenteral Nutrition. 2009 “All patients who are not expected to be on normal nutrition within 3 days should receive parenteral nutrition within 24 to 48 hours if enteral nutrition is contraindicated or if they cannot tolerate enteral nutrition.” Society of Critical Care Medicine and American Society of Parenteral and Enteral Nutrition. 2009 “Use of parenteral nutrition should be reserved and initiated only after the first 7 days of hospitalization (when EN is not available).”
  4. 4. Objectives EPaNIC Study Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients • To compare the effect of late initiation of parenteral nutrition with early initiation on rates of death and complications in adults in the ICU who are at risk but not chronically malnourished • To investigate whether preventing a caloric deficit during critical illness by providing PN early in disease course would reduce the rate of complication or whether withholding PN for 1 week would be clinically superior
  5. 5. Methods Study Design • Prospective • Randomized • Controlled • Parallel-group • Multi-centered Study Population • 4640 Underwent Randomization • 2313 – Early Initiation • 2328 – Late Initiation • Patients stratified according to diagnostic categories • Subjects were not blinded
  6. 6. Methods Inclusion Criteria • Score of 3 or more on the Nutritional Risk Screening • 18 years or older • BMI of at least 17 Exclusion Criteria • Short-bowel syndrome • Home ventilation • Pregnant or Lactating • Enrollment in another trial • Readmission to the ICU
  7. 7. Baseline Characteristics • Well matched between groups (Table 1) • Sex, Age, Weight, BMI • Disease States: Diabetes Mellitus, Dialysis-dependent Kidney Failure, Cancer, Nutritional Risk Screening Score • Emergency Admission • Severity of Illness by APACHE II Scoring • Scale of 0 to 71 • Sepsis diagnosed by the ACCP Society of Critical Care Medicine Criteria • Score calculated by trained experts
  8. 8. Study Procedure All Patients • Enteral Nutrition if unable to eat by Day 2 • Twice daily increase in infusion rate • Prokinetic agents • Duodenal feeding tubes • Parenteral administration early in the ICU stay to avoid micronutrient depletion on re-feeding • Trace elements • Minerals • Vitamins
  9. 9. Study Procedure Early Initiation Group • Day 1: 20% IV Glucose Solution • Target total daily energy intake of 400 kcal • Day 2: 20% IV Glucose Solution • Target total daily energy intake of 800 kcal • Day 3: Initiation of PN • Target: 100% of caloric goal (EN and PN) • Maximum caloric goal for all patients: 2880 kcal per day.
  10. 10. Study Procedure Late Initiation Group • Day 1-7: 5% Glucose solution in a volume equal to parenteral nutrition • Day 8: Parenteral nutrition administration if enteral nutrition proved insufficient
  11. 11. Study Procedure Administration and Monitoring • Patient-data-management system used to calculate daily volumes of EN and PN for each patient • After discharge from the ICU, nutritional management at the discretion of attending physicians • Continuous Insulin infusion • Glucose goal: 80-110 mg/dL • Blood Gas analyzer to monitor ABG every 1-4hours
  12. 12. Data Collection • Intensive care treatments and procedures • New bacterial or fungal infections • Chemical Analysis Results • Blood • Urine • Hematologic Studies • Inflammation markers • Total Energy Intake by EN and PN
  13. 13. Data Collection • Therapy Interruptions • Feeding Related Complications • Functional Status before discharge • Direct Health Care costs • Patient invoices • Analyzed from healthcare payer perspective • Government and patient costs • Vital Status 90 days after randomization
  14. 14. Outcome Measures Primary Endpoint • Duration of dependency on intensive care • Number of ICU days • Time to discharge from the ICU • Defined as time patients were ready for ICU discharge, to avoid bias Safety Endpoints • Vital Status • Proportion alive at ICU discharge in 8 days or less • Rates of ICU and Hospital deaths • Rates of survival up to 90 days • Rates of complications and hypoglycemia
  15. 15. Outcome Measures • Number of patients with new infections • Infection site • Duration of Antibiotic Therapy • Inflammation (C-reactive Protein max) • Time to final weaning from mechanical ventilatory support • Duration of hospital stay and time to discharge • Functional status • Distance walked in 6 minutes • Proportion of patients independent in all ADLs Secondary Endpoints
  16. 16. Outcome Measures • Rate of acute renal injury • RIFLE Criteria (Risk, Injury, Failure, Loss, End-stage) • Doubling of the SrCr level from admission • Proportion of patients requiring renal replacement therapy • Duration of the therapy in the ICU • Need for and duration of pharmacologic or mechanical hemodynamic support Secondary Endpoints
  17. 17. Outcome Measures • Proportion of patients presenting with liver dysfunction • Total Bilirubin >3mg/dL • GGT >79.5Units/L • Alkaline phosphatase >405 Units/L • ALT >123 • AST>114 • Incremental Healthcare costs from randomization to discharge Secondary Endpoints
  18. 18. Statistical Analysis • Sample size • Ability to detect a between-group change of 1 day in the ICU stay • Power at least 80% • Ability to detect a change of 3% in the rate of death • Power of at least 70% • Intention-to-treat Analysis • Two-sided p value of less than 0.05 to indicate statistical significance • Use of JMP Software for analysis
  19. 19. Statistical Analysis Variable Test Used Data Comparison • Chi-squared Test • Student’s T-Test • Non-parametric testing • Median Test • Wilcoxon Rank-sum Test • Mann-Whitney U Test Healthcare Costs • Student T Tests Time-To Event • Analysis: Kaplan Meier Methods • Effect Size: Cox-proportional Hazards
  20. 20. Results • Insulin Requirements to reach target • Late: 31 IU (Interquartile 19-48) • Early: 58 IU (Interquartile 40-85) • Glucose Level • Late: 102 ± 14 mg/dL • Early: 107 ± 18 mg/dL • P <0.001 Study Intervention
  21. 21. Results 6.1% 10.4% 11.2% 18.2% 6.3% 10.9% 11.2% 18.8% 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% 14.0% 16.0% 18.0% 20.0% Death in ICU Death In Hospital Death Within 90 Days Nutrition-related Complications Safety Outcomes Late Early
  22. 22. Results 75.2% 71.7% 69.0% 70.0% 71.0% 72.0% 73.0% 74.0% 75.0% 76.0% Discharged Alive in 8 days p = 0.007 Late Early 3.5% 1.9% 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% 3.5% 4.0% Hypoglycemia during intervention p = 0.001 Statistically Significant Safety Outcomes
  23. 23. Results Median days • Late – 3 (2-7) • Early – 4 (7-9) • P = 0.02 Duration greater than 3 days • Late – 48% • Early – 51.3% • P= 0.02 Primary Outcome Duration of dependency on Intensive Unit care Hazard Ratio for time To discharge from the ICU • 1.06 • 95% CI between 1.00 and 1.13 • P= 0.04
  24. 24. Results Kaplan-Meier Estimates Proportion Discharged from ICU Proportion discharged alive from ICU
  25. 25. Results Kaplan-Meier Estimates Discharged from Hospital Discharged Alive from Hospital
  26. 26. Results 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% Secondary Outcome – New Infections Late Early
  27. 27. Results 140 150 160 170 180 190 200 Max CRP (mg/L) Secondary Outcome - Inflammation Late Early More pronounced acute inflammatory response in the late Initiation group (p<0.001)
  28. 28. Results Median Duration of Selected Secondary Outcomes 0 2 4 6 8 10 12 14 16 18 Mechanical Ventilation (p=0.02) Renal Replacement Therapy (p=0.008) Hospital Stay (p=0.004) Time(days) Late Early
  29. 29. Results Kidney Failure • Percentage with Modified RIFLE Category • Late – 4.6% • Early – 5.8% • P = 0.06 • Percentage requiring Renal Replacement therapy • Late – 8.6% • Early – 8.9% • P= 0.77 Mechanical Ventilation • Percentage of patients requiring MV for >2days • Late – 36.3% • Early – 40.2% • P = 0.006 • Hazard ratio for discharge alive from hospital: 1.06 • 95% CI = 1.00-1.13
  30. 30. Results Functional Status at Discharge • Distance on 6 minute walk test • Late (624 pts) – 277 meters • Early (603 pts) – 283 meters • P = 0.57 • Percentage of patients independent in all ADLs • Late (1060 pts) – 73.5% • Early (996 pts) – 75.5% • P= 0.31 Hospital Stay • Percentage in the hospital for >15 days • Late – 45.5% • Early – 50.1% • P = 0.001 • Hazards ratio for time to discharge alive from the hospital: 1.06 • 95% CI = 0.99 – 1.12
  31. 31. Results 16,863 17,973 € 16,000 € 16,500 € 17,000 € 17,500 € 18,000 € 18,500 Mean Total Incremental Health Care Cost P =0.04 Late Early • Included in Total Cost Calculation • Cost billed to government • Costs billed to patient • From randomization to discharge • Values do not include deduction of cost of PN in the late-initiation group
  32. 32. Results Subgroup Analysis
  33. 33. Study Limitations • No glutamine or immune-modulating compounds • Low protein-to-energy ratio due to standardized, premixed parenteral nutrition products • Subjects and providers were aware of study group assignments
  34. 34. Author’s Conclusions “Early initiation of parenteral nutrition appears to be inferior to the strategy of with-holding until Day 8 while providing vitamins, trace elements, and minerals. Late initiation was associated with fewer infections, enhanced recovery, and lower healthcare costs ”
  35. 35. Journal Critique
  36. 36. Title and Abstract Strong • Title reflective of study and objectives • Abstract well organized Weak • Results regarding acute inflammation and hypoglycemia not addressed in abstract
  37. 37. Methods Strong • IRB Approved • Appropriate Study Duration • Patients stratified according to 16 diagnostic criteria • 7 Participating ICUs Weak • Site locations? • Trace elements, vitamins and minerals given to both groups
  38. 38. Outcomes and Statistical Analysis Strong • IRB Approved • Safety Outcomes included • Analysis by computer software • Sub-group analysis performed Weak • Too many secondary outcomes • Intention-to-treat analysis vs per-protocol
  39. 39. Results Strong • Establishes 1-day difference in ICU stay between groups • Distinguishes results between overall hospital stay and ICU stay • Graphs and charts provided are helpful Weak • Article mentions few results of the stated secondary outcomes • Reader must refer to supplementary appendix
  40. 40. Conclusions Strong • Supported by the collected data • Study limitations addressed Weak • Late-initiation group short-comings not addressed • Hypoglycemia • Hyperbulirubinemia
  41. 41. Overall Impression Benefits of Late Initiation of TPN therapy • Fewer ICU infections • Shorter duration of mechanical ventilation • Shorter course of renal-replacement therapy • Shorter ICU and hospital stay • Reduced Health care costs Disadvantages of Late Initiation of TPN therapy • Higher degree of acute inflammation • Increase in hypoglycemic episodes
  42. 42. References • Zeigler TR. “Parenteral Nutrition in the Critically Ill Patient”. N Eng J Med. 2009;361:1088-1097. • Casaer MP, Dieter M, Hermans G, et. al. “Early versus Late Parenteral Nutrition in Critically Ill Adults”. N Eng J Med. 2011; • Singer P, Berger MM, Van den Berghe G, et al. “ESPEN guidelines on parenteral nutrition: Intensive Care”. Clin Nutr 2009;28:387-400. • Martindale RG, McClave SA ,Venek VW, et al. “Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive summary”. Crit Care Med, 2009;37:1757-61.

×