feeding in critical care

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”


• 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


• 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



>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

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)


• 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.


• 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?

feeding in critical care

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