Transcript A Randomized Trial of Empiric Antibiotics and Invasive
Rupinder Dhaliwal, RD
Nutrition & Rehabilitation Investigator’s Consortium Clinical Evaluation Research Unit Queen’s University, Kingston General Hospital
Conflicts of Interest
I have received speaker honoraria or been paid from grants from the following companies: – Nestlé Canada – Fresenius Kabi AG – Baxter – Abbott Laboratories
Objectives
• Describe rationale for the novel components of the PEP uP protocol
Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients :
• Review results of cluster trial using PEP UP Protocol • Describe strategies to effectively implement this protocol in the ICU
Current Practice in ICUs in 2011
120 100 80 60 40 20 0 1 2 3 4 Mean of All Sites 5 6 7 8
ICU Day
Best Performing Site 9 10 11 12 Worst Performing Site n =211 ICUs, mean intake 56% prescribed calories Heyland et al INS 2011 unpublished data
Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake!
Association Between 12-day Caloric Adequacy and 60-day Hospital Mortality Optimal amount = 80-85% Heyland DK, et al. Crit Care Med. 2011;39(12):2619-26.
Failure Rate
% high risk patients who failed to meet minimal quality targets (80% overall energy adequacy)
91.2
87.0
78.1
75.6
75.1
69.8
79.9
Heyland et al Unpublished observations Results of 2011 International Nutrition Survey (INS)
Can we do better?
A shift in the feeding paradigm is needed!
PEP UP Protocol: components
Early enteral nutrition Goal rate feeding in stable patients Trophic feeds Feeding unstable patients Motility agents Higher gastric residual volumes Protein supplements Semi-elemental formula Monitor nutritional adequacy
Early EN (within 24-48 Hours of Admission) Is Recommended!
Optimal amount of protein and calories for critically ill patients?
Initial Efficacy and Tolerability of Early EN with Immediate or Gradual Introduction in Intubated Patients
N = 100 pts mechanically ventilated pts (not in shock) to immediate goal rate vs gradual ramp up
Desachy A, et al. Intensive Care Med. 2008;34(6):1054-9.
“Trophic Feeds”
Progressive atrophy of villous height and crypt depth in absence of EN.
Leads to increased permeability and decreased IgA** secretion.
Can be preserved by a minimum of 10-15% of goal calories.
Observational study of 66 critically ill patients suggests TPN † + trophic feeds associated with reduced infection and mortality compared to TPN alone 1 .
A = No EN; B = 100% EN 1 Marik. Crit Care & Shock. 2002;5:1-10; Ohta K, et al. Am J Surg. 2003;185(1):79-85.
Initial Tropic vs. Full EN in Patients with Acute Lung Injury
The EDEN randomized trial Rice TW, et al. JAMA. 2012;307(8):795-803.
Trophic vs. Full EN in Critically Ill Patients with Acute Respiratory Failure
The EDEN randomized trial
Despite no differences in clinical outcomes……….
“Survivors who received initial full-energy EN were more likely to be discharged home with or without help as compared to a rehabilitation facility (68.3% for the full-energy group vs. 51.3% for the trophic group;
p
= .04).”
Rice TW, et al. Crit Care Med. 2011;39(5):967-74.
What about feeding the hypotensive patient?
Resuscitation is the priority No sense in feeding someone dying of progressive circulatory failure However, if resuscitated yet remaining on vasopressors:
Safety and efficacy of EN??
Feeding the hypotensive patient?
Prospectively collected multi-institutional ICU database of 1,174 patients who required mechanical ventilation for more than two days and were on vasopressor agents to support blood pressure.
Khalid I, et al. Am J Crit Care. 2010;19(3):261-8.
The beneficial effect of early feeding is more evident in the sickest patients, i.e., those on multiple vasopressor agents
Pro-motility Agents
Conclusion:
1) Motility agents have no effect on mortality or infectious complications in critically ill patients 2) Motility agents may be associated with an increase in gastric emptying, a reduction in feeding intolerance and a greater caloric intake in critically ill patients “Based on 1 level 1 study and 5 level 2 studies, in critically ill patients who experience feed intolerance (high gastric residuals, emesis), we recommend the use of a pro motility agent”.
2009 Canadian CPGs www.criticalcarenutrition.com
It’s Not Just About Calories...
Inadequate protein intake Loss of lean muscle mass Immune dysfunction Weak prolonged mechanical ventilation So in order to minimize this, we order:
Protein supplement Beneprotein ® 14 grams mixed in 120 mls sterile water administered BID via NG
113 select ICU patients with sepsis or burns On average, receiving 1,900 kcal/day and 84 grams of protein No significant relationship with energy intake but…
Allingstrup MJ, et al. Clin Nutr. 2012;31(4):462-8.
The PEP uP Protocol
Stable patients should be able to tolerate goal rate We use a concentrated solution to maximize calories per ml
Begin 24 hour volume-based feeds
Feeding Schedule.
. After initial tube placement confirmed, start
Peptamen® 1.5
. Total volume to receive in 24 hours =
Peptamen® 1.5 at 10 ml/h
after initial tube placement confirmed. Reassess ability to transition to 24 hour volume-based feeds next day. {
Intended for patient who is hemodynamically unstable (on high dose or escalating doses of vasopressors, or inadequately resuscitated) or not suitable for high volume EN (ruptured AAA, upper intestinal anastomosis, or impending intubation)}
just use trophic feeds Note indications for trophic feeds NPO.
Please write in reason:
__________________ ______. (only if contraindication to EN present:
bowel perforation, bowel obstruction, proximal high output fistula. Recent operation and high NG* output not a contraindication to EN.)
Reassess
ability to transition to 24 hour volume-based feeds next day.
Doctors need to justify why they are keeping patients NPO We want to minimize the use of NPO but if selected, need to reassess next day Note, there are only a few absolute contraindications to EN
Single centre pilot study Heyland DK, et al. Crit Care 2010. 2010;14(2):R78
PEP UP Protocol: other components
Gastric residual volume threshold 300 mls or more ( REGANE Study 500 ml vs 250 mls safe Montejo et al 2010 Int Care Med ) Protein supplement Beneprotein ® 14 grams mixed in 120 mls sterile water administered BID via NG until full EN Motility agents are started immediately, rather than started when there is a problem – – – – Maxeran ® 10 mg IV q 6h (halved in renal failure) Reassess need for motility agents daily If still develops high gastric residuals, add erythromycin 200 mg q 12h Can be used together for up to 7 days but should be discontinued when not needed any more – Reassess need for motility agents daily
24 Hour Volume-based goal vs Hourly rate
•
Make up for missed hours over the remaining hours
•
Max 150 ml/hr
•
RN latitude to adjust
A Change to Nursing Report
Please report this % on rounds as part of the GI systems report Adequacy of nutrition support = 24 hour volume of EN received Volume prescribed to meet caloric requirements in 24 hours
Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol
A multi-center cluster randomized trial
Research Questions
What is the effect of the new
innovative feeding protocol
, (PEP uP protocol), combined with a
nursing educational intervention
on EN intake compared to usual care? What is the
safety, feasibility and acceptability
of the new PEP uP protocol?
Hypothesis: this aggressive feeding protocol combined with a nurse-directed nutrition educational intervention
will be safe, acceptable
, and effectively
increase protein and energy
delivery to critically ill patients.
Design
Control Baseline
6-9 months later
Follow-up
18 sites (low performing from survey)
Intervention Protocol utilized in all patient mechanically intubated within the first 6 hours after ICU admission Focus on those who remained mechanically ventilated > 72 hours
Tools to Operationalize the PEP uP Protocol
Bedside Written Materials
EN initiation orders Gastric feeding flow chart Volume-based feeding schedule
Description
Physician standardized order sheet for starting EN.
Flow diagram illustrating the procedure for management of gastric residual volumes.
Table for determining goal rates of EN based on the 24 hour goal volume.
Excel spreadsheet used to monitor the progress of EN.
Daily monitoring checklist
Materials to Increase Knowledge and Awareness
Study information sheets PowerPoint presentations Self-learning module Posters Frequently Asked Questions (FAQ) document Electronic reminder messages Monthly newsletters Information about the study rationale and guidelines for implementation of the PEP uP protocol. Three versions of the sheets were developed targeted at nurses, physicians, and patients’ family, respectively.
Information about the study rationale and how to implement the PEP uP protocol. A long (30-40 minute) and short (10-15 minute) version were available.
Information about the PEP uP protocol and case example to work through independently.
A variety of posters were available to hang in the ICU during the study.
Document addresses common questions about the PEP uP Protocol.
Animated reminder messages about key elements of the PEP uP protocol to be displayed on a monitor in the ICU.
Monthly circular with updates about the study.
Analysis
3 overall analyses: – ITT* involving all patients (n = 1,059) – Efficacy analysis involving only those that remain mechanically ventilated for > 72 hours and receive the PEP uP protocol (n = 581) – Those initiated on volume-based feeds (n = 57) * ITT: intention to treat
45 ICUs with < 50% nutritional intake in 2009 International Nutrition Survey assessed for eligibility 18 Randomized
Flow of Clusters (ICUs) and Patients Through the Trial
9 assigned to intervention group 522 patients met eligibility requirements and were enrolled and included in ITT analysis. 197 on MV ≤ 72 hours 54 did not receive the PEP uP protocol 271 patients included in efficacy analysis 57 patients initiated on 24 hour volume feeds 9 assigned to control group 537 patients met eligibility requirements and were enrolled and included in ITT analysis. 231 on MV ≤ 72 hours 306 patients included in efficacy analysis
Participating Sites
Hospital type
Teaching Non-teaching
Size of hospital (beds)
Mean (range)
ICU structure
Open Closed
Case type
Medical Neurological Surgical Neurosurgical Trauma Cardiac surgery Burns Other
Size of ICU (beds)
Mean (range)
Full time equivalent dietician (per 10 beds)
Mean (range)
Regions
Canada USA
Intervention (n = 9)
4 (44.4%) 5 (55.6%) 396.9 (139.0, 720.0) 3 (33.3%) 6 (66.7%) 9 (40.9%) 3 (13.6%) 5 (22.7%) 2 (9.1%) 1 (4.5%) 0 (0.0%) 1 (4.5%) 1 (4.5%) 12.6 (7.0, 20.0) 0.5 (0.3, 0.9) 4 (44.4%) 5 (55.6%)
Control (n = 9)
4 (44.4%) 5 (55.6%) 448.7 (99.0, 1000.0) 4 (44.4%) 5 (55.6%) 9 (36.0%) 2 (8.0%) 8 (32.0%) 2 (8.0%) 2 (8.0%) 1 (4.0%) 1 (4.0%) 0 (0.0%) 16.3 (8.0,25.0) 0.4 (0.0, 0.6) 5 (55.6%) 4 (44.4%)
p-values
1.00
0.97
1.00
0.97
0.12
0.76
1.00
Patient Characteristics (n = 1,059) n Age
Mean
± SD
Sex
Male (%)
Admission category
Medical Elective surgery Emergent surgery
Admission diagnosis
Cardiovascular/vascular Respiratory Gastrointestinal Neurologic Sepsis Trauma Metabolic Hematologic Other non-operative conditions Renal-operative Gynecologic-operative Orthopedic-operative Other operative conditions
Intervention Baseline Follow-up 270 252
65.1 ± 15.5
157 (58.1%) 230 (85.2%) 14 (5.2%) 26 (9.6%) 40 (14.8%) 110 (40.7%) 35 (13.0%) 19 (7.0%) 37 (13.7%) 0 (0.0%) 11 (4.1%) 1 (0.4%) 7 (2.6%) 2 (0.7%) 1 (0.4%) 1 (0.4%) 6 (2.2%) 64.1 ± 16.7
137 (54.4%) 222 (88.1%) 12 (4.8%) 18 (7.1%) 43 (17.1%) 112 (44.4%) 19 (7.5%) 19 (7.5%) 20 (7.9%) 2 (0.8%) 15 (6.0%) 0 (0.0%) 15 (6.0%) 0 (0.0%) 0 (0.0%) 1 (0.4%) 6 (2.4%)
APACHE II score
Mean
± SD 23.0 ± 7.2
23.5 ± 7.1
Control Baseline Follow-up 270 267
63.4 ± 15.1
170 (63.0%) 213 (78.9%) 23 (8.5%) 34 (12.6%) 31 (11.5%) 78 (28.9%) 29 (10.7%) 30 (11.1%) 57 (21.1%) 17 (6.3%) 13 (4.8%) 0 (0.0%) 5 (1.9%) 0 (0.0%) 0 (0.0%) 1 (0.4%) 9 (3.3%) 21.1 ± 7.3
61.4 ± 16.2
173 (64.8%) 212 (79.4%) 23 (8.6%) 30 (11.2%) 51 (19.1%) 81 (30.3%) 29 (10.9%) 28 (10.5%) 25 (9.4%) 18 (6.7%) 6 ( 2.2%) 1 (0.4%) 7 (2.6%) 3 (1.1%) 1 (0.4%) 3 (1.1%) 12 (4.5%) 21.1 ± 7.3
p-value
0.45
0.56
0.24
un defined 0.53
Patient Nutrition Assessment Information (All patients – n = 1,059)
n Height
Mean
± SD
Weight
Mean
± SD
Body mass index (kg|m2)
Mean
± SD
Prescribed energy intake (kcals)
Mean
±
SD
Prescribed protein intake (g)
Mean
±
SD
Prescribed energy intake by weight (kcals|kg)
Mean
±
SD
Prescribed protein intake by weight (g|kg)
Mean
±
SD
Intervention Baseline Follow-up
1.7 81.0
270
28.6 1,776.6 ± 352.4
86.0
23.3 1.1 ± ± ± ± ± ± 0.1
25.3
8.2
22.2
5.9
0.3
1.7 81.4 28.6 1,774.8 86.0 23.2 1.1
252
± ± ± ± ± ± ± 0.1
26.3
9.6
339.3
19.8
5.9
0.3
Baseline Control Follow-up 270 267
1.7 ± 0.2
83.5 ± 26.5
29.1 ± 8.1
1,768.6 ± 412.1
99.9 ± 29.6
22.1 ± 4.9
1.2 ± 0.3
1.7 ± 0.1
83.7 ± 22.6
28.6 ± 7.0
1,784.4 ± 387.9
100.1 ± 27.8
22.3 ± 5.5
1.2 ± 0.3
p-value
0.55
0.77
0.96
0.82
0.09
0.79
0.26
Clinical Outcomes
(All patients – n = 1,059) Length of ICU stay (days)* Length of hospital stay (days)* Length of mechanical ventilation (days)* Patient died within 60 days of ICU admission
Median (IQR Median (IQR) Median (IQR) Yes † )
Intervention Baseline Follow-up
6.1 (3.4,11.1) 14.2 (8.1,29.8) 3.7 (1.6,9.1) 70 (25.9%) 7.2 (3.4,11.1) 13.5 (8.1,28.4) 4.3 (1.3,9.9) 68 (27.0%) 6.4 16.7
Control Baseline
(3.3,12.6) (7.5,27.7) 3.1 (1.4,8.4) 65 (24.1%) * Based on 60-day survivors only. Time before ICU admission is not counted.
Follow-up
5.7 (2.8,11.8) 13.8 (7.1,26.6) 3 (1.4,7.3) 63 (23.6%)
p-value
0.35
0.73
0.57
0.53
† IQR: interquartile range
Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites
(All patients) % Calories Received/Prescribed Intervention sites Control sites
p value <0.0001
p value = 0.001
p value = 0.71
373 360 Baseline 390 375 Follow-up Baseline 362 380 Follow-up
Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites
(All patients) % Protein Received/Prescribed Intervention sites Control sites
p value <0.0001
p value = 0.005
p value = 0.81
331 371 Baseline 375 371 Follow-up Baseline 378 379 359 377 Follow-up
Daily Proportion of Prescription Received by EN in ITT, Efficacy and Full Volume Feeds Subgroups (Among Patients in the Intervention Follow-up Phase)
ITT Efficacy Full volume feeds n ITT n Ef f icacy n FVF 243 113 57 219 113 57 194 113 57 171 108 54 153 105 52 138 96 46 118 83 40 107 75 35 83 59 26 76 52 23 59 40 17 52 35 14 1 2 3 4 5 6 7 ICU Day 8 9 10 12 ITT Efficacy Full volume feeds n ITT n Ef f icacy n FVF 243 113 57 219 113 57 194 113 57 171 108 54 153 105 52 138 96 46 118 83 40 107 75 35 83 59 26 76 52 23 59 40 17 52 35 14 1 2 3 4 5 6 7 ICU Day 8 9 10 12
Compliance with PEP uP Protocol Components (All patients n = 1,059)
100 90 80 70 60 50 40 Intervention - Baseline Control - Baseline Intervention - Follow-up Control - Follow-up 30 20 10 0
Supplemental Protein (ever) Supplemental Protein (first 48hrs) Motility Agents (ever) Motility Agents (first 48hrs)
Difference in Intervention baseline vs. follow up and vs. control all <0.05
Peptamen 1.5
Complications
(All patients – n = 1,059)
15 13 11 5 3 9 7 1 -1
p
> 0.05
Intervention - Baseline Control - Baseline Vomiting
Vomiting
Intervention - Follow-up Control - Follow-up Regurgitation
Regurgitation
Macro Aspiration
Macro Aspiration
Pneumonia
Pneumonia
Nurses’ Ratings of Acceptability
24 hour volume based target Starting at a high hourly rate Starting motility agents right away Starting protein supplements right away Acceptability of the overall protocol After Group Mean (Range)
8.0 (1-10) 6.0 (1-10) 8.0 (1-10) 9.0 (1-10) 8.0 (1-10)
1 = totally unacceptable and 10 = totally acceptable
Overall, how acceptable is this new PEP uP feeding protocol to you?
Need more instructions to include all staff members Too much confusion over what protocol was supposed to be May need a few adjustments however I think its overall acceptable Good if everyone knows how to do it Initial starting dose is too high Maybe we needed more awareness by the MDs
Barriers to Implementation
Difficulties embed into EMR* Non-comprehensive dissemination of educational tools
Facilitators to Implementation
Involvement of nurse educator (nurses owned it) Ongoing bedside encouragement and coaching by site dietitian * EMR: electronic medical records
PEP uP Trial Conclusion
Statistically significant improvements in nutritional intake – Suboptimal effect related to suboptimal implementation Safe Acceptable Merits further use Can successfully be implemented in a broad range of ICUs in North America
Learning from the Trial : Next Steps
Change PEP uP protocol first day order to simplify (25 ml/hr for day 1) Improve documentation of protein supplements (add to MAR!) Develop PEP uP collaborative (community of practice) – PEP uP demonstration sites – Revise and disseminate tools Audit practice again in early 2013
Introduce PEP uP in YOUR ICU!
Call to action – is there room and interest to improve feeding practice in your ICU?
Identify nutrition champions – RNs, MDs, RDs Feeding successfully requires a team approach Education – – Comprehensive education of the entire ICU team is essential Tools and resources are available at criticalcarenutrition.com
Ongoing monitoring/feedback
Education and Awareness Tools
PEP uP Pocket Guide PEP uP Poster
Protocol to Manage Interruptions to EN Due to Non-GI Reasons Can be downloaded from
www.criticalcarenutrition.com
PEP uP Monitoring Tool
Prompts for high risk patients improving calorie and protein intakes (≥ 80% prescribed) starting motility agents, small bowel feeding, supplemental PN