feeding in critical care
TRANSCRIPT
Nutritional Support & Post-op Bowel Management
Benjamin Braslow, MD, FACS Division of Traumatology, Emergency General
Surgery & Surgical Critical Care Department of Surgery
University of Pennsylvania School of Medicine
Nutrition Overview
• Historical Aspect • Who, When, How to Feed? • Calorie/Protein Needs • Overfeeding • Nitrogen Balance • SCC Practice Guidelines
History of Nutrition Support - Enteral
• Ancient Egypt (3000-500 BC) – rectal • Earliest devices
Pipe or hollow tube w/ a bladder tied to one end Evolved to flexible leather catheter in 1790
• Nutrients fed included: wine, brandy, milk, whey, grain broths, beef/chix broth, raw eggs
• 1617 silver tube thru the nostril used to feed into nasopharynx to treat tetanus patients Nasal feeding used for “conscious and at least
partially cooperative patients”
History of Nutrition Support - Enteral
• 1890 President Garfield fed rectally for 79 days after an assassination attempt
• 1918 Andersen fed patients jejunally on the operating table
• 1939 Ravdin & Stengel – tie 2 tubes together to simultaneously decompress stomach and feed into jejunum
History of Nutrition Support - Enteral
• 1947 Reigel & Rhoads – demonstrate +N2 balance with enteral feeding w/in 5 days post-op
• 1952 Fallis & Barron place naso-jejunal tubes weighted with toy balloons filled with 2-5 ml of mercury attached with cat gut suture that then dissolved
• Rectal feeding was used up until WWII but by then gastric or SB feeding were preferred
Rhoad’s Beagle pups grow bigger (TPN) than orally-fed (ad lib Chow) paired littermates
History of TPN circa 1965-1971
History of TPN
• 1st Infant in US (CHOP) with small bowel atresia doubled weight in 75 days on TPN
glucose and protein only oils rubbed on skin to promote absorption of EFAs
History of TPN
• First 6 adult TPN patients • Fed 2850 glucose kcal/d, 113 gm
protein/d (no Fat) • +4 gm nitrogen balance
Dudrick & Rhoads Surg 64:134, 1968
Malnutrition and Surgical Risk
• Studley, JAMA 106:458,1936 Chronic peptic ulcer patients 2x in post-op mortality with pre-op
weight loss > 20% wound dehiscence, pneumonia
Demonstrated Dangers of Hypoproteinemia
• Rhoads, Ann NY Acad Sci 63: 268, 1955 Vomiting Delayed GI motility Wound rupture due to poor fibroplasia Delayed callus formation in experimental bone
fracture ↑ hemorrhagic shock ↓ resistance to infection
VA Pre-Op TPN Study Buzby, et al. NEJM 1991
• 1991 PRCT of 395 malnourished patients • 7-15 d pre-op TPN + 3 d post-op vs. no TPN
No difference in major complications or mortality 2.2 x in infectious complications for mild-
moderately malnourished (<95% IBW, alb < 3.9, pre alb < 17)
Severely malnourished (% wt loss, serum alb, TLC) who received TPN had fewer non-infectious complications & no difference in infections Mean pre-op nutrient intake 2994 kcal/d (450-4543)
or ~ 45 kcal/kg • For severely malnourished surgical patients, 7-15
days of pre-operative TPN improves outcomes
Increase in both surgical morbidity & mortality related to mildly depleted albumin.
Gibbs et al Arch Surg 1999
Goals of Nutrition Support Provide substrate for growth, repair, & maintenance of body function
• Consistent with metabolic state • Avoid metabolic derangements • Preservation of immune function • Promote nitrogen retention
• Diminish metabolic response to stress (loss of LBM) • Improve patient outcomes
– morbidity / mortality – patient performance – resource utilization
Nutrition Guidelines
When to Start Nutrition?
• Healthy/Well-nourished/Elective Surgery Inadequate oral intake > 7-10 days
Braunschweig et al, Am J Clin Nutr, 2001;74:534-542. • Critical illness
Initiate w/in 5 days Earlier in stressed/malnourished pts
• Potential benefits of early enteral nutrition American Society of Parenteral and Enteral Nutrition (ASPEN)
Guidelines for Use of Parenteral & Enteral Nutrition in Adults, 2009, JPEN
Nutrition for Poets
• The human body has a biochemical engine (metabolism) that mixes oxygen with an organic fuel (e.g., carbohydrates) at high temps, and this releases energy from the fuel that is then used to power the human body.
What is Your Patient’s Malnutrition Status?
Malnutrition Evaluation***
Moderate Malnutrition Severe Malnutrition Intake Evaluation
Illness/Injury Acute Chronic Soc/Envir Acute Chronic Soc/Envir Intake over time >7 days w/
<75% intake >30 days w/ <75% intake
>90 days w/ <75% intake
>5 days w/ <50% intake
>30 days w/ <75% intake
>30 days with <50% intake
Weight Loss Evaluation Weight Loss
History 1-2% over 1 week >2% over 1 week 5% over 1 month >5% over 1 month
7.5% over 3 months >7.5% over 3 months 10% over 6 months >10% over 6 months
20% over 1 year >20% over 1 year Other Evaluation
Fat Loss Yes or No (less severe) Yes or No (more severe) Muscle Loss Yes or No (less severe) Yes or No (more severe)
Edema Yes or No (less severe) Yes or No (more severe) Grip Strength reduced reduced
Journal of the Academy of Nutrition & Dietetics. 112(5):730-8, 2012 May
**Must meet 2 or more criteria to qualify as Moderate or Severe Malnutrition
Calorie Needs: Gold Standard Indirect Calorimetry
• All patient populations • Requires a metabolic cart • Based on measurements of CO2 production and
O2 consumption • Determines Respiratory Quotient (RQ)
0.8-0.9 indicates mixed fuel consumption • Limitations
– Nasal cannula oxygen (unmeasured O2 input) – FiO2 >60%
Respiratory Quotient (RQ = Vco2produced / Vo2consumed)
• Fat: RQ 0.70, 9.1 kcal/g • Protein: RQ 0.80, 4.0 kcal/g • Mixed Fuel : RQ .85 (GOAL) • Carbohydrate: RQ 1.0, 3.7 kcal/g • >1.0 Lipogenesis/overfeeding
increased CO2 production fatty liver metabolic alterations
– Example
1g Glucose + .74 L of O2 -----> .74 L of CO2 + 3.75kcal of energy
Calorie Needs- Estimated Harris-Benedict Formula • Based on gender, height, weight, and age for
estimating Resting Energy Expenditure (REE) REE female = 655 + 9.6 (weight in kg) + 1.85 (Ht in cm) – 4.7 (age in years) REE male = 66.5 + 13.8 (weight in kg) + 5.0 (Ht in cm) – 6.8 (age in years) Modified REE for Acute Care Surgery Patient = 1.5 (REE)
• Most accurate for hospitalized patients per HUP CNSS data Harris JA, Benedict FG, Publication 279, Carnegie Institute of Washington,
Washington DC, 1919
Quick Method = 20-30 non protein kcal/kg/d
Assessing Calorie Needs: Predictive Equations
• Penn State Equation – ICU patients • Swinamer Equation – ICU patients • Harris-Benedict Equation – non-intubated
patients • Mifflin-St. Jeor Equation – obese,
ambulatory patients
• On average, 20-30 calorie/kg
• Underfeeding: lipolysis ------> muscle wasting (deltoids, temporal, orbital, clavicular)
• Overfeeding : Lipogenesis ----------> increased CO2 production, impaired vent weaning hepatic steatosis (shunting fat into liver, NASH) metabolic alterations (hyperglycemia, hyperlipidemia)
Non-Protein Calories • Carbohydrate (~ 4 kcal/gm)
• In aqueous solution: dextrose = 3.4 kcal/g glucose = 3.7 kcal/g
Max rate of Glucose Oxidation = 4-5 mg/kg/min in critical illness (~7gm/kg/day) Maintain blood glucose 80-140 mg/dl 60-70% non-protein kcal
• Fat (Enterally ~ 9 kcal/gm…Parenteral ~10 kcal/gm due to presence of emulsifiers and glycerol)
Max dose = 2.5 g/kg/day < 1.0 gm/kg – critical illness Maintain TG <400mg/dl 30-40% non-protein kcal
Calorie Requirements - Obesity
• 50% of ICU patients with BMI > 30 Tremblay, Chest, 2003; 123:1202-7.
• No data on appropriate kcals for obese patients 30% of excess weight is fat free mass
(metabolically active tissue / lean body mass) Foster, Metabolism, 1988; 37:467-72.
• Goal is to support fat free mass
Protein Needs • 1gm Protein = 4 Kcal Energy • Healthy adult
0.8-2.0 gm/kg maintenance (depends on lifestyle) • Critical Illness (MICU)/Elective Surgery
1.5-2.0 gm/kg repletion • Trauma/Emergency Surgery
~2-2.5g/kg Varies by disease state, comorbid conditions
• Assess utilization with nitrogen balance
Protein in Renal and Liver failure
• Renal Failure 1.3gm/kg no dialysis 1.5gm/kg hemodialysis 2.0gm/kg CVVHD/PD
• Liver Failure 0.6 –0.8 gm/kg
encephalopathy 1-1.5 gm/kg compensated
cirrhosis BCAA if Stage IV Hepatic Encecephalopathy (metabolized more
effectively by hepatocytes)
Metabolic Changes after Stress
Surgery/Trauma
Proteolysis Lipolysis Glycogenolysis
Epinephrine Norepinephrine Glucagon Cortisol
Cytokine release: Tumor necrosis factor IL-1, IL-2, IL-6
CATABOLISM Up-regulation of inflammatory response •Negative acute phase reactants include:
•albumin, prealbumin, transferrin
•Positive acute phase reactants include: •C-reative protein, complement , coagulation and fibrinolytic systems, ferritin
Malnutrition and Lung Function • Protein calorie malnutrition:
Increased risk of pneumonia, respiratory failure Impaired respiratory muscle function Decreased respiratory muscle mass Decreased ventilatory drive
Clinical Nutrition, 1998;17:7-10.
Protein Assessment
• Weekly Albumin (21d) , Prealbumin (2-3d) , Transferrin (8-10d) , RBp (12hrs-limited utility)
’d by inflammatory response, stress & surgery Follow trends…Single value not useful.
• Nitrogen balance • Wound healing • Clinical improvement (vent wean, activity)
Protein Loss in Critical Illness • First 25 days after trauma
Loss of 16% total body protein (p <0.0002) 67% protein loss from skeletal muscle
Annals of Surgery 1996;223(4): 395-405.
• Similar protein losses in trauma and sepsis Trauma pts – 14.6% total body protein Sepsis pts – 13.1% total body protein
**Protein loss greatest in first 10 days Annals of NY Acad Sciences 2000;904:592-602.
• Acute muscle wasting in first week of critical illness More severe with multiorgan failure Up to 15% muscle loss in 1st week w/ 4-organ failure Increased breakdown and decreased synthesis
JAMA 2013;310(15):1591-1600.
Nitrogen Balance • Objective measure of nitrogen (protein) retention • Traditional N Balance = Nintake – (UUN + 4)
24 hr urine collection for urine urea nitrogen 4 = insensible protein losses (~ 4gm/d)
• Stool (diarrhea • Sweat • Skin slough • Mucosal slough • High fistula output (increase fudge factor)
Requires >500 ml urine/day Stable nutrition regimen x 48 hrs prior Begin 7am - End 7am
Nitrogen Balance
• Nutrition Regimen: 175g pro, 500 fat, 500
gluc Convert protein to N2 175g pro/6.25g N2 =28g
N2
28g IN
• 24hr UUN results: 19.86 g/TV Insensible losses: 4g Wound drainage
(500ml): 1g 24.86g OUT
N2 Balance: IN (28g) – OUT (24.86g) = +3g N2
Goal is +2 to +4g
Nitrogen Balance in Open ABD
• The open abdomen represents a significant source of protein /nitrogen loss in the critically ill.
• Failure to account for this loss in nutritional calculations may lead to underfeeding and inadequate nutritional support.
• Estimate of 2g of nitrogen per liter of abdominal fluid output.
• NB = Nintake- (UUN + 4 + 2 (Abd Fluid Output in L) )
Cheatham et al. CCM 2007 vol.35, no. 1
Non-Protein Calorie : Nitrogen Ratio to Prevent Catabolism
• Normal / Healthy Person = 150 :1
• Catabolic / SICU patient = 80-100 : 1
Starvation vs. Metabolic Stress
Starvation Adaptive
Stress
Resting Energy Expenditure Protein Breakdown
Urinary Nitrogen Loss
Fuel Source Fat Mixed (Pro, CHO, Fat)
If the gut works, use it!
How to Feed?
Enteral (TEN) vs. Parenteral (TPN)
• Enteral nutrition preferred method of nutrition support Prevents gut atrophy Decreases intestinal permeability May reduce bacterial translocation TPN ?Risk factor for sepsis, MSOF ASPEN Guidelines, JPEN, 2009:26(1S):90SA-92SA.
Normal intestinal villus, during fed state
Deterioration of gut integrity from gut disuse
McClave. J of critical illness. 2001:16:198-202;
Early Enteral Nutrition vs. TPN Author Population Outcomes: TPN vs. TEN
Moore et al, 1989, Journal of Trauma
59 pts with abdominal trauma
•20% increase in septic morbidity •17% increase in intra-abdominal sepsis and pneumonia
Kudsk et al, 1992, Ann Surg
98 pts with abdominal trauma
•20% higher incidence of pneumonia •10% increase in intra-abdominal abscess
Moore et al, J Trauma, 1989;29:916-924 Kudsk et al, Ann Surg, 1992;215:503-513.
Outcomes: TPN vs. TEN Author # Trials Outcomes Heyland, JAMA 1998
Meta-analysis 26 RCT (n=2211 pts) Surgical or Critically ill TPN vs PO diet & IV Dextrose
•No mortality difference with TPN •Trend towards fewer complications with TPN •Possible role for malnourished surgical pts
Braunschweig, Am J Clin Nutr 2001
Meta-analysis 27 PRCT (n=1828 pts) TPN vs EN vs. PO diet Medical & surgical
•Lower infection risk with EN vs. TPN •Malnourished pts higher risk of mortality/ infection
Peter, CCM 2005 Meta analysis of 30 RCT (n= ??pts) Early EN vs. early TPN
•No difference in mortality •EN pts had shorter LOS (1.2 days) •Higher infection rate with TPN
Outcomes: TPN vs. TEN Author # Trials Outcomes Koretz RL et al. AM J Gastroenterology 2007
Meta-analysis 44 RCT Surgical pts TEN vs No nutr support, TEN vs TPN , Oral feeds vs no artificial nutrition
•No mortality differences •TEN assoc w/ lower rates of infection •TEN assoc w/ fewer major complications •TEN asoc w/ shorter hosp LOS
Gastric versus Post-pyloric
• Gastric access easier to achieve • Contraindications to gastric feeds:
Severe pulmonary compromise? GCS <9 (relative) Persistent high gastric residuals (>200ml) or
high output (>500ml/24hrs) Inability to maintain HOB >30° (Absolute)
• Gastric intolerance Post-pyloric feeds
Gastric vs. Small Bowel Feeds • Gastric Feeds
Easy to obtain access
Longer time to goal? 43.8 hrs vs.. 22.6 hrs1
Higher aspiration risk? Continuous gastric feeds a
risk factor for nosocomial pneumonia2
• Small Bowel Feeds More difficult access
Faster advance to goal 22.6 hrs vs.. 43.8 hrs1
Fewer GI complications
No significant difference in pneumonia rate3
1Kortbeek et al, J Trauma, 1999;46:992-998. 2Artigas et al, Crit Care Med, 2001;29:304-309. 3Montejo et al, Crit Care Med, 2002(30):796-800.
Summary
• Enteral nutrition preferential Attempt to feed early Gastric or small bowel Monitor for intolerance
• Enteral nutrition failure TPN Inability to tolerate >60% goal Persistent GI symptoms
Enteral Nutrition Tolerance • Abdominal exam
Abdominal distention and/or pain ?1st warning of small bowel ischemia
Nausea/Vomiting No BM
• Residuals - Gastric Hold for residual >200ml on 2 consecutive occasions Replace residual
• Intervention Prokinetic agent Advance tube to post-pyloric position Bowel regimen
Enteral Nutrition Tolerance
• Diarrhea defined >5 BM / day >500 ml stool
output/day Stool output > TEN
intake
• Diarrhea treatment Check medications Check C. difficile Lactobacillus Immodium (C. diff -) Fiber (psyllium) Peptide based elemental
Indications for TPN
• Paralytic ileus (greater than 5-7 days) • Mesenteric ischemia • Small bowel obstruction • High output fistula (unless enteral access
placed distal to fistula) • Intolerance to enteral nutrition therapy or
without enteral access • Short Bowel Syndrome
Complications of TPN
• Increased infectious risk Line sepsis, gut atrophy
• Metabolic abnormalities Hyperglycemia, hypertriglyceridemia Refeeding syndrome Electrolyte derrangements TPN equivalent to ~1/4 NSS
• Fluid Overload • Hepatic Steatosis • Cholestasis
Vitamins & Trace Elements
• Standard in TPN Multivitamin (includes 150 micrograms Vitamin
K..matches oral diet) Trace elements
Copper, manganese, selenium, chromium, zinc • Supplemental Vitamins:
Wound Healing 50 mg Vitamin C, 5 mg Zinc
Alcohol Abuse 100 mg Thiamine, 1 mg Folate
Inflammation Injury x 4-6 days:
Wound exudation and fibrin clot formation, neutrophils remove bacteria,
macrophage activity
Proliferation 3-5 days post-injury x 2-3 weeks:
Epithelialization, angiogenesis, fibroblast proliferation, collagen deposition and crosslinking,
wound contraction
Remodeling 2-3 weeks post-injury x 2 yrs:
Collagen maturation and stabilization, development of tensile strength
Normal Wound Healing
Thompson et al, NCP, 2005;20:331-347.
Vitamin A
Vitamin C
Zinc
Vitamins and Minerals • Vitamin A
Deficiency impairs wound healing Impaired collagen synthesis and cross-linking
Indication for supplementation: Vitamin A deficiency Glucocorticoid administration (first 2-4 days after
insult) High vitamin E supplementation Radiation/Chemotherapy Diabetes
Contraindications: Renal or liver failure Protein deficiency
Vitamins and Minerals • Zinc
Deficiency: wound strength reduced, collagen synthesis decreased, slower rate of epithelialization
Indications for supplementation: Only effective in deficient state Increased losses – wound drainage, ostomy, diarrhea
Toxicity: Impaired copper status (necessary for crosslinking) Reduced wound healing
Vitamins and Minerals • Vitamin C
Deficiency: impaired collagen cross-linking, reduced wound tensile strength, increased wound dehiscence
Indication for supplementation: Deficiency – expensive to test Doses of 100mg – 2000mg recommended
– Exact dose unclear – Higher doses for more increased wound severity – Renal failure – limit of 250 mg/day
Specialty Nutrients
• Arginine Conditionally essential amino acid Studies demonstrate increased collagen
deposition, improved nitrogen balance Results inconclusive ?Safety in sepsis/critical illness
– May promote inflammation More research needed
Specialty Nutrients
• Glutamine Primary fuel source for rapidly dividing
cells Some data support improved nitrogen
balance, improved immune function after surgical stress
More research needed for definitive recommendations
TPN Additives
• Regular Insulin Insulin added by Pharmacy **Add insulin conservatively ½ - 2/3 prior day’s insulin requirement SSI for remaining coverage Never use TPN as conduit for insulin GTT
• No other additives allowed
Zantac – order IV dose, not in TPN Sandostatin NOT compatible with TPN
Lipid Tolerance
• If Triglyceride < 400 --parenteral lipid “OK” • Triglyceride > 400
Saturates lipoprotein lipase which exports TG from hepatocytes Lower or remove fat from TPN Recheck TG in 2 days
• Hypertriglyceridemia frequently seen in uncontrolled hyperglycemia, pancreatitis, & sepsis
TPN Complications
• Refeeding Syndrome • Fluid overload • Electrolyte abnormalities
TPN equivalent to ~ 1/4 to ½ NSS • Hyper/Hypoglycemia • Blood stream infections • Hepatobiliary complications (stasis)
Refeeding Syndrome--ATP Depletion
• Treatment Correct electrolyte abnormalities before starting
or advancing TPN / TEN Give volume & energy slowly Monitor vitals, I/O
√Lytes, Mg, Phos, ionized Ca++ twice daily
Vitamin supplementation as appropriate Avoid overfeeding
Medication/Fluid Issues
• Drug/Nutrient Interactions Phenytoin (p.o.), Levofloxacin (p.o.) Hold tube feeding 2 hours before and after Protein in TEN competes for absorption Adjust TEN goal rate prn
• Hidden Macronutrients Dextrose - drips, peritoneal dialysis, CVVHD Lipid – diprivan/propofol: hold fat from TPN
Hot Topics In Nutrition
• Enteral Feeding on Pressors • Permissive Underfeeding • Glucose Control (tight vs. lenient) • Immune-Modulating Nutrients
Glutamine, Arginine, BCAA, Omega-3 FAs, Selenium
ALL YOU NEED TO SUCCEED
•Critical Care Nutrition Guidelines from the Canadian Clinical Guidelines Practice Group. http://www.criticalcarenutrition.com/index.php?option=com_content&view=category&layout=blog&id=25&Itemid=109
Any Questions ?
Post-op Ileus • Old School: (origin: Greek ‘eileos’ – twisting)
Any obstruction of the intestines (i.e. gallstone ileus, meconium ileus)
• 2012: Profound disturbance of bowel motility that is often clinically indistinguishable from bowel obstruction and frequently the result of a noxious or injurious insult
Primary ileus: inevitable response to surgical trauma (resolving w/in 2-3 days) Paralytic Postop ileus: ileus lasting more than 3 days
after surgery
Post-op Ileus--$
• Most common reason for delayed hospital discharge following abdominal surgery
• > $1,000,000,000 in US Bosio et al… Semin Colon Rectal Surg 16:235– 238 2005
• In one review of patients undergoing hemicolectomy, prolonged postoperative ileus increased the duration of hospitalization by an average of 8 days with additional median costs of $14,904
Salvador C, et al. 2005 Pharm Ther (P&T) 30:590–595
Post-op Ileus….Teleology
• Does this seemingly obligatory period of GI quiescence have some protective benefit ?
• Are attempts to assuage the duration and severity only challenging nature?
Post-op Ileus: Clinical Picture
• Generally…operations that involve: Large incisions Extensive manipulation of the intestines Exposure of the peritoneum to irritants
• Blood • Pus • Stool
• Characterized by: lack of coordinated intestinal activity Substantial overall reduction in peristalsis
Post-op Ileus: Clinical Picture
• Variable signs & symptoms
Sometimes asymptomatic Cramping Abdominal pain Nausea Bloating / no flatus Bilious emesis Anorexia
• Phys Ex Abdominal distention Tympany or Dullness Non-specific tenderness +/- bowel sounds
Post-op Ileus: Diagnostics
• Diagnostic studies generally not necessary in early post-op period
• No diagnostic test can confirm or exclude the diagnosis of post operative ileus w/ certainty
KUB may demonstrate dilated air filled loops of SB and colon…non-specific finding
• > POD #5 CT / UGI useful in differentiating ileus vs.
mechanical obstruction and identifying causative agents
• Abscess • Anastamotic leak • Adhesions • Inflamation • intussusception
ADYNAMIC ILEUS
SBO
Post-op Ileus: Resolved?
• Traditional endpoint = passage of flatus or BM Based on fact that colonic motility is last to
recover • SB return to normal peristalsis 12-24 hrs • Stomach 24-48 hrs • Colon 3-5 days Livingston. Dig Dis Sci 1990
• No evidence that PO feeds need to be held until colonic motility has recovered.
Post-op Ileus: Resolved? • Return of bowel sounds?
Not reliable Presence = propulsive activity May signify SB activity w/o return of colonic fxn
Holte et al. Br J Surg 2000
• NGT output? Unreliable Overly conservative measure of bowel function Positionally dependant Change from green (bilious) to clear more indicative of normal
bowel transit • Flatus
Requires a conscious patient who is comfortable reporting its occurrence to investigator
Post-op Ileus: Resolved?
• The most physiologic indication that an ileus has resolved is the patient’s ability to tolerate oral / enteral intake without pain, bloating or emesis.
• Best test: Trial of oral / enteral intake
Risk of emesis Risk of aspiration
Normal Physiology of GI Motility
• Fasting state: Peristaltic activity of stomach and small intestine characterized by slow (q1-2hrs), irregular, waves of contractility (MMC migrating motility complex)
1st described in 1969 by Szurszewski Housekeeper fxn by propelling intraluminal contents distally
• Fed state: More forceful, frequent, and regular peristaltic waves of contraction.
#, intensity, and duration depend on amt and chemical composition of food ingested
• Colonic motility marked by slow rhythmic contractions that vary little between fasting and fed states
Can be slowed by both internal and extrinsic factors Main fxn is to store feces and absorb water
Luckey et al. Mechanism and treatment of post-operative ileus. Arch Surg 2003
Pathogenesis
Pathogenesis
• Autonomic nervous system Parasympathetic activity
(Vagal input) stimulates bowel activity by inducing release of acetylcholine in the myenteric plexus
Sympathetic activity reduces
acetylcholine release and inhibits bowel motility
Pathogenesis
• Afferent neural input due to irritation or inflammation of the peritoneum results in increased sympathetic efferent neural activity via splanchnic nerves
• Balance of power shifts to sympathetic ….overall in gut activity
Kenwater J. Acta Physiol Scand 1965
GI Hormones & Neurotransmitters • Although Motilin and VIP play important role in
regulation of gut motility…Exact mechanism in ileus unknown
• Attempts to modify the activity of gut hormones and
NTs to decrease post-op ileus have been moderately successful in animal models but inconclusive in human studies.
– Substance P antagonists – NO synthesis inhibitors – Calcitonin gene-related peptide (CGRP) receptor antagonists – Corticotropin-releasing factor (CRF) receptor antagonists
Inflammatory Mediators • Tissue trauma leads to release of cytokines and other
inflammatory mediators…. Decreased GI motility Kalff et al. Surgical manipulation of the gut elicits an intestinal muscularis
inflammatory response resulting in post-surgical ileus. Ann Surg 1998
• Techniques designed to minimize inflammation (MIS, gentle tissue handling) appear to minimize post-op ileus
-Davies et al. Lap colectomy shortens ileus in canine model. Surgery 1997 -Schwenk et al. Lap vs. Open colectomy (humans) Langenbecks Arch Surg 1998 -Chen et al. Lap vs open colectomy (Humans) Dis Colon Rectum 2000
• 166 pts Cleveland Clinic FL
-Leung et al. Systemic cytokine response after Lap assisted rsxn of rectosigmoid carcinoma Ann Surg 2000
Maximally Invasive Surgery
Inflammatory Mediators
• Ketorolac use beneficial in reducing post-op ileus ? Anti inflammatory effect ? Overall opiate-sparing effect
Ferraz et al. Nonopiod analgesics shorten duration of POI. Am Surg 1995
Anesthesia
• All types of general anesthesia have an effect on bowel motility Exert their strongest effects on region of
bowel most dependant on neural integration Colon more susceptible to inhibitory actions
of anesthetics • Devoid of intercellular Gap junctions Livingston. Dig Dis Sci 1990
Post-op Narcotic Analgesia • Opioids
Inhibitory effect on gastric motility • Increase tone in antrum & D1
Slow SB transit / Decreased colonic motility • Rx w/ MSO4 receptor antagonist (Methylnaltrexone)
compared with placebo significantly reduces morphine-induced delay in the gastrointestinal transit time and the peripheral side effects of morphine therapy
Yuan CS, Foss JF (2000) Oral methylnaltrexone for opioid- induced constipation. JAMA 284:1383–1384
• New µ- receptor antagonist ADL-8-2698 also promising Taguchi et al. NEJM 2001…….FDA approved 2008
Peripheral µ antagonist: ADL 8-2698, Alvimopan (Entereg®)
• Restricted to the gut -very little systemic absorption -unable to cross blood-brain barrier -competitively binds to µ-opioid receptor in the
gastrointestinal tract with higher binding affinity than methylnaltrexone
PCEA • Administration of a local anesthetic through a mid-
thoracic (T6-T8) epidural cath may decrease post op ileus.
Disruption of afferent inhibitory signals from abdominal viscera Reduction of sympathetic neural input Increased blood flow to gut Anti-inflammatory effect of local anesthetic absorbed systemically
Kehlet H, et al . Lancet 2003 Steinbrook RA, et al. Anesth Analg 1998
• Effect not seen with low thoracic or lumbar catheters • Epidural vs systemic narcotics….Epidural wins.
Mann C, et al. Anesthesiology 2000
• Most efficacious = bupivacaine alone w/o narcotic
Treatment
• Old School: Bowel rest & NGT decompression – Kehlet et al. Care after colonic operation –is it
evidence based? Results from a multinational survey in Europe and th U.S. JACS 2006
NGT Decompression ?
• The routine use of NGT decompression after abd surgery is no longer recommended
• Routine use is associated with higher pulmonary complication rates
• Exceptions: some gastric and duodenal procedures Rare patient who develops severe ABD
distention or intractable vomiting Park et al. Early removal of NGT after cystectomy w/ urinary
diversion: does POI risk increase? Urology 2005 Nelson et al. Systematic review of prophylactic NG decompression
after abdominal operations. Br J Surg 2005 Nelson et al. Prophylactic NG decompression after abd surgery.
Cochrane Database Sys Rev 2005 Cheatham et al. a meta-analysis of selective vs routine NG
decompression after elective laparotomy. Ann Surg 1995
Ambulation ?
• Although early post-op ambulation has a strong clinical bias Does prevent atelectasis Does reduce PNA rates Does prevent DVT Does not appear to expedite resolution of
post-op ileus Waldhausen et al. Ann Surg 1990
NPO ? • Early small enteral feedings (w/in 24hrs) actually stimulate
GI tract and reduce period of post-op ileus safe No increase in anastomotic leaks or intra abd abscess prevents an increase in gut mucosal permeability produces a positive nitrogen balance Improves wound healing
Carr CS, et al. BMJ 1996 Reissmann P, et al. Ann Surg 1995 Di Fronzo LA, et al. Arch Surg 1999 Cutillo G, et al. Obstet Gyn 1999 Sands DR, et al. Nutrition 1999 Mangesi L, et al. Cochrane Database Syst Rev 2002
Gum Chewing ?
• Sham feeding in form of chewing gum has been reported to speed recovery after elective colon surgery
Fitzgerald et al. World J of Surg (2009) --Systematic review and meta analysis… 7 studies with 272 pts Asao T, et al. JACS 2002 - s/p Lap colectomy Schuster R, et al. Arch Surg 2006 - s/p open sigmoid
rsxn
Pharmacologic Agents • Despite numerous trials no single GI motility
agent has been shown to be especially effective. • Metoclopramide (Reglan):
Dopamine antagonist / cholinergic agonist Often successful in Tx of postop N/V Despite prokinetic effects, has not been shown to sig
effect duration of postop ileus Jepsen S, et al. Br J Surg 1986 Cheape JD, et al. Dis Colon Rectum 1991 Seta ML, et al. Pharmacotherapy 2001
• In 2009, the U.S. FDA required all manufacturers of metoclopramide to issue a black box warning regarding the risk of tardive dyskinesia with chronic or high-dose use of the drug�
Pharmacologic Agents
• Erythromycin Macrolide ABX / Motilin agonist Randomized studies confirm improvement in
gastric emptying (Janssens J, et al. NEJM 1990)
In randomized , placebo-controlled , double blinded study of 134 pts undergoing colorectal surgery…did not alter recovery from post-op ileus (Smith AJ, et al. Dis Colon Rectum 2000)
Pharmacologic Agents
• Laxatives & Rectal Suppositories May be helpful in reducing postop ileus but can
cause cramping, abdominal pain, and bloating No good RCDB studies out there Recent non randomized , unblinded study of 20
women s/p rad hysterectomy Rx’d w/ bid MOM and qD dulcolax suppositories
• 50% reduction in time to first flatus • 50% reduction in hosp LOS (4 vs 8 days)
Pharmacologic Agents • Neostigmine:
Reversible inhibitor of acetylcholinesterase Prevents breakdown of acetylcholine in synaptic cleft Increases colonic motility in early postop period in pts
undergoing colorectal surgery Kreis ME, et al. Surgery 2001
Never shown to reduce overall duration of post-op ileus. • Cissapride
Serotonin agonist Mixed results Removed from market for assoc w/ potentially fatal
arrhythmias.
Pharmacologic Agents
• Over recent decades several drug therapies have been promoted as potentially beneficial in the amelioration of postoperative ileus.
• A recent Cochrane review of prokinetic agents in this setting studied 39 randomized controlled trials and showed that the use of many of these agents (including erythromycin, cholecystokinin, cisapride, and dopamine antagonists) is not supported by the available evidence
Traut U et al (2008) Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults. Cochrane Database Syst Rev (Online) 1:CD004930
ANY QUESTIONS?