TPN and Acute Pancreatitis

Acute Pancreatitis
Stephen J D O’Keefe
University of Pittsburgh Medical
School

Learning Objectives
Upon completion of this session, you
should be able to:
1. Understand the pathophysiology of
acute pancreatitis
2. Know when to use nutritional support
3. Determine the best method of
nutritional support

Learning Assessment
Questions
1. The best way of meeting nutritional requirements
without stimulating the pancreas is to use jejunal
feeding (true/false)
2. The achievement of nutritional balance early in
the course of acute pancreatitis has been shown
to improve outcome (true/false)
3. Patients with acute pancreatitis are at higher risk
than other critically ill patients for developing
hyperglycemic complications (true/false)

Nutritional concerns
Elevated requirements
• Protein catabolism: increased 80%
• Energy expenditure: increased 20%
Nutritional risks
• Food stimulated pancreatic autodigestion
• Pancreatic endocrine impairment – hyperglycemia
and hypertriglyceridemia
Sepsis risk - immunoparesis

Enteral or Parenteral?
! Enteral is physiological
! Parenteral is not
! but enteral stimulates trypsin secretion
and may exacerbate acute
pancreatitis, while parenteral does not

Enteral Nutrition in Acute
Pancreatitis
! Pancreatic stimulation occurs in 3
phases
– Cephalic
– Gastric
– Intestinal

Ileal brake

Amylase Secretion in
Healthy Volunteers
i units/h
25000
22500
20000
17500
15000
12500
10000
7500
5000
2500
0
amyl
O’Keefe et al. Am J Physiol 2003
Oral
IV
Placebo

TPN and Acute
Pancreatitis
! Controlled study: TPN vs IV fluids; ; Sax
et al. Am J Surg 1987:
– 54 patients with mild disease (av(
RC=1),
TPN group did worse
! LOS 16 vs 10 days
! Catheter sepsis 11 vs 2%

Glycemic Response: Enteral
vs Parenteral
170
160
150
140
mg/dl
130
120
110
100
90
elemental
intravenous
80
Some of 0 Some of 120 Some of 240
O’Keefe et al. Am J Physiol 2003

Trypsin Secretion
1200
1000
i units/h
800
600
400
Elemental enteral
Complex enteral
200
0
true try
O’Keefe et al. Am J Physiol 2003

Trypsin Secretion
in health & disease
Units/hr
700
Group means (SE): p

Distal Jejunal Feeding
Vu et al. Eur JCI 1999

Why Enteral Feeding is
Superior
! Nutrients are needed in the
splanchnic, not the systemic
circulation
! Enteral feeding suppresses the
systemic inflammatory response

TPN enhances endotoxin-
induced cytokine production
Fong et al. Ann Surg 1989
! 12 healthy volunteers
! Randomized to enteral or parenteral
feeding for 7 days
! Arterial, hepatic vein and femoral
catheters
! IV E Coli endotoxin challenge

TPN enhances endotoxin
induced cytokine production
and hypermetabolism
TPN group:
! TNF alpha higher
! CRP higher
! Epinephrine levels higher
! Protein catabolism higher

9
8
7
6
5
4
3
2
1
0
patients
controls
umol/Kg/min
13C-leucine flux
D3-leucine flux
splanchnic leucine flux

Enteral vs Parenteral
Nutrition: mild
McClave et al: JPEN 1997
! 30 pts, 32 studies randomized to EN (jejunal
Peptimen) ) or PN after 48h.
! Mean Ranson’s 1.3 (0-5)
– i.e. mild
! Not intention to treat: 8 excluded for feeding
failure, 4 for failure to place or tolerate tubes
Results: No diff in nutrition days (5-7d), LOS,
infections
! Stress-hyperglycemia more common with PN
(p

Enteral vs Parenteral
Nutrition: mild-severe
Windsor et al: Gut 1998
! 34 patients, 16 EN, 18PN
! EN: severe pts (6/16) jejunal feeding, rest
oral!
! EN received less energy
Results: CRP & APACHE 2 down only with EN
! Endotoxin abs increased with PN
! MOF in 5 PN pts
! IA sepsis in 3 PN pts
! Only PN pts needed ICU management!

Enteral vs Parenteral
Nutrition: severe
Kalfarentzos et al: B J Surg 1997
! It took 5 years to accrue 40 patients with
necrotizing pancreatitis
! 72h IVI, imipenen
! Diets: jejunal peptide formula 25cc/h, inc
every 4h, TPN 40cc/h, inc every 4 h: target
1.5-2g
prot, , 30-35Kcal/kg/d
35Kcal/kg/d
Results: nitrogen balance achieved in both
! Septic and total complications higher with
TPN
! Cost x3 lower with EN

MCV Study: 12 month
evaluation of nutritional
management
All acute pancreatitis admissions
48hr IV fluids & analgesia
n=154
Improved
oral diet
n=102
No improvement
Randomized
Jejunal feeding
n=26
TPN & bowel rest
n=25
Abou-Assi, O'Keefe. Gastroenterol 2001

Hospitalization & Nutrition Support Days
22.5
days
20
17.5
15
12.5
10
7.5
5
2.5
*
* = p

Quantity of Feeds Received
100
90
% of requirements
80
70
60
50
40
***
***
ENTERAL
PARENTERAL
30
20
10
0
% Kcal % prot

Nutrition-Associated
Complications
! Hyperglycemia needing insulin: EN 2,
PN 7 (p

Summary
! Most patients (75%) do not need
nutritional support.
! duration of nutritional support is shorter
with enteral feeding
! TPN provides more nutrition, but causes
more hyperglycemic and septic
complications
! Enteral feeding saves $2,362/pt

Interventional Tube-
Feeding
! Nasogastic
! Nasojejunal
1. Fluoroscopic
2. Endoscopic
! Percutaneous
1. Surgical G and J
2. Endoscopic G with J extension
3. Direct endoscopic J

Transnasal Endoscopic
Placement of Feeding Tubes
in the ICU
51 ICU patients referred for TPN
– 29% respiratory failure, 28% head injury, 33%
acute pancreatitis
! Results:
– successful ‘StayPut‘
StayPut’ ’ placement in 46/51
– Perfect concordance between re-endoscopy endoscopy and
X-ray confirmation of placement
– Unrecognized esophageal and gastric pathology
revealed in 60%
– TPN avoided in 77%
! O’Keefe et al. JPEN Sept 2003

Upper Abdominal Pain
Serum Enzymes >3x
Normal
NPO, IV Fluids, Analgesics
for 48 hrs
Jejunal Tube Placement
Elemental Diet 20 cc/hr
Progress to Goal over 48
hrs
Better
No improvement/
worse
Tolerated
Not
Tolerated
Improved Abdominal Pain
&
Serum Enzymes
Distal
jejunal
tube
Progressive Oral Diet
Discharge
TPN

Enteral Feeding in Necrotizing
Pancreatitis:
pt 1: 74 yr old man
! “when the tube feeding rate was
advanced to 60cc/h (65g protein,
1440 Kcal), abdominal pain
returned the following day,
associated with a dramatic
increase in WBC to 32.3 x10 9 /l. A
repeat CT suggested further
necrosis of the head, neck and
body, with marked fat stranding
and increased fluid collection.
Peripancreatic fluid was aspirated
(70cc of chocolate fluid), and
shown to be non-infected. Tube
feeding was held and TPN was
restarted, allowing provision of full
nutritional requirements (i.e. 140g
protein, 2080 Kcal/day) within 3
days, with a dramatic improvement
in WBC from 32.3 to 9.3 x109/l”
! O’Keefe et al. Clin Gastro Hepatol
July 2003

Effects of Enteral Feeding in
Necrotizing Pancreatitis
7000
Enteral feeding
6000
5000
4000
3000
trypsin x 10 (iu/h)
amylase (iu/h)
lipase (iu/h)
2000
1000
0
30
60
90
120
150
180
210
240
270
300
330
360

Incorporation of 13 C-labeled Leucine
into Secreted Trypsin
9
8
7
atoms% excess
6
5
4
3
2
healthy voln 13C
acute pancreatitis 13C
1
0
Fig 4
minutes
0
30
60
90
120
150
180
210
240
270
300
330
360
370

Enteral Feeding in Necrotizing
Pancreatitis:
pt 2: 18 yr old woman
1400
22000
units/h
1200
1000
800
600
AMYLASE
units/h
20000
18000
16000
14000
12000
LIPASE
400
200
0
30
60
90
120
150
180
210
240
270
300
330
360
minutes
10000
8000
6000
4000
30
60
90
120
150
180
210
240
270
300
330
360
Minutes
IV......................Enteral..........................................................
IV......................Enteral..........................................................
180
160
140
120
units/h
100
80
60
TRYPSIN
40
20
0
-20
30
60
90
120
150
180
210
240
270
300
330
360
minutes
IV......................Enteral..........................................................

Conclusions
! The superiority of enteral feeding to
TPN in the management of acute
pancreatitis is due to
– Targeted delivery of nutrients to the
splanchnic bed and prevention of
bacterial overgrowth
– Avoidance of TPN complications

Learning Assessment
Questions: Answers
1. False it is difficult to meet nutritional
requirements with jejunal feeding, and only distal
jejunal feeding avoids pancreatic stimulation
2. False although this statement may be correct,
no controlled studies have been conducted to
prove it
3. True patients with acute pancreatitis have both
exocrine and endocrine damage, leading to a
relative insulin deficiency

References
1. O’Keefe
SJD, Lee RB, Anderson FP, Gennings C, Abou-Assi
Assi S, Clore JN, Heuman D,
Chey W. The Physiological Effects of Enteral and Parenteral Feeding on Pancreatic P
Enzyme Secretion in Humans. Am J Physiol 2003;284:27-36
36
2. Abou-Assi
Assi SA, O’Keefe SJD. Nutrition in Acute Pancreatitis. J Clin Gastroenterol
2001;32(3):203-209
209
3. McClave S, Greene L, Snider H, Makk LJ, Cheadle WG, Owens NA, Dukes LG,
Goldsmith LJ. Comparison of the safety of early enteral vs. parenteral nutrition in
mild acute pancreatitis. J Parent Ent Nutr 21, 014 – 020, 1997.
4. Windsor ACJ, Kanwar S, Li AGK, Barnes E, Guthrie JA, Spark JI, Welsh F, Guillou PJ,
Reynolds JV. Compared with parenteral nutrition, enteral feeding attenuates the
acute phase response and improves disease severity in acute pancreatitis. Gut 1998;
42: 431- 435.
5. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is
superior to parenteral nutrition in severe acute pancreatitis: results r
of a randomized
prospective trial. British Journal of Surgery 1997, 84, 1665 – 1669
6. Abou-Assi
Assi S, Craig K, O’Keefe SJD. Hypocaloric jejunal feeding is better than TPN in
acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol.
2002;97(9): 2255-2262
2262
7. O'Keefe SJ, Foody W, Gill S. Transnasal endoscopic placement of feeding tubes in the
intensive care unit. J Parenter Enteral Nutr. . 2003 Sep-Oct;27(5):349
Oct;27(5):349-54. 54.
8. O’Keefe SJD, Broderick T, Turner MA, Stevens S, O’Keefe JS. Nutrition in the
Management of Necrotizing Pancreatitis. Clin Gastroenterol Hepatol. . 2003;1:315-321
321