postoperative ileus - pathophysiology and clinical implications

postoperative ileus

pathophysiology and clinical implications

postoperative ileus

• most pronounced after colonic surgery

• duration– stomach: 24-48 hours – small intestine: 0-24 hours – colon: 48-72 hours

• associated with– increased hospital stay– delayed feeding and mobilisation– patient discomfort

Holte and Kehlet, Br J Surg 2000; 87: 1480

* p<0,05

effect of epidural local anesthetics vs. systemic opioids on postoperative ileus

* ** ** *

050

100150200

Wal

lin (1

986)

Sche

inin

(198

7)

Ahn

(198

8)W

attw

il (19

89)

Bred

tman

(199

0)Ri

war (

1991

)

L iu

(199

5)Ne

udec

ker (

1999

)

Leng

th o

f PI

(hou

rs)

Epidural local anesthetics Systemic opioid


* p<0,05* p<0,05

* p<0,05

***

020406080

100120

Leng

th o

f PI (

hour

s)

Epidural bupivacaineEpidural opioid

* p<0,05

effect of epidural bupivacaine vs. epidural opioid on postoperative ileus


* p<0,05

* P < 0,05

effect of epidural bupivacaine-opioid vs. systemic opioid on postoperative ileus

??

**

*

*

?

0

40

80

120

160Hjor

tso (

1985

)Se

eling

(199

0)J a

yr (1

993)

L iu (1

995)

Mann (

2000

)Ca

rli (2

001)

Norris

(200

1)Pa

ulsen

(200

2)

Leng

th o

f PI (

hour

s)

Epidural bupi/opioid

Epidural or systemic opioid

Holte and Kehlet, Br J Surg 2000; 87: 1480Kehlet and Holte, Am J Surg 2001; 182: 5SHolte and Kehlet, Drugs 2002; 62: 2603

p<0,05

epidural analgesia and postoperative ileus

• epi-LA vs. systemic opioid • epi-LA vs. epi-opioid • epi-LA/opioid vs. systemic opioid

Jorgensen et al., The Cochrane Library, Issue 4, 2001

effect of surgical manipulation on

0

0,2

0,4

0,6

0,8

1

0 0,1 1 10 100 300

Betanechol uM

cont

ract

ility

ControlLaparotomyEventrationRunningCompression **

*

*

0200400600800

Cont

rol

Lapa

roto

my

Even

trat

ion

Runn

ing

Com

pres

sion

Kalff et al., Ann Surg 1998; 228: 652

intestinal contractility leukocyte infiltration in intestinal mucosa

* p<0,05

inflammatory mediators that inhibit gastrointestinal motility

• nitric oxide (NO)• substans P• VIP• 5-hydroxytryptamine• calcitonine gene-related peptide• CRF• prostaglandines (some subtypes)

Kehlet, World J Surg 1999; 23: 801

*p<0,05

laparoscopic colonic surgery and postoperative ileus

**

020406080

100120

Dura

tion

of P

I (ho

urs) Laparoscopy

Open surgery

Holte and Kehlet, Drugs 2002; 62: 2603

* p<0,05

randomized studies

gastrointestinal tubes and postoperative ileus

no effect(increase in fever and atelectasis)

Cheatham et al., Ann Surg 1995; 221: 469Sagar et al., Br J Surg 1992; 79: 1127

* p <0,05

effect of metoclopramide on postoperative ileus

0306090

120

Leng

th o

f PI (

hour

s) metoc lopramideplacebo


pharmacologic strategies in preventing PI

propanolol -dihydroergotamine -neostigmine -erythromycin -cisapride cholecystokinin -ceruletide vasopressin -

Holte and Kehlet, Drugs 2002; 62: 2603

laxatives and postoperative ileus

• one randomized study with bisacodyl– decrease in postoperative ileus (25 vs. 56 h)

• need further evaluation in randomized trials

Olsen et al., Ugeskr Laeger 1985; 147: 3070

* p<0,05

early oral feeding and postoperative ileus

** *

0306090

120

Dura

tion

of P

I (ho

urs)

Early feeding

Traditional feeding


* p<0,05

*

* **

0

2

4

6

8

10

gastricemptying

flatus bowelmovement

hospital stay

time

(day

s)

high fluidlow fluid

Lobo et al., Br J Surg 2001 suppl; 88: 25

•randomized, controlled trial•2*10 patients•major colonic surgery

postoperative fluid regimenshigh fluid: > 3L water and 150 mml Na/daylow fluid: < 2L water and 75 mmol Na/day

* p< 0,05

fluid administration and postoperative ileus

mobilisation and postoperative ileus

no effect

Waldhausen et al., Ann Surg 1990; 212: 671

opioids and postoperative ileus

• endogenous opioids

• exogenous opioids

• kappa-agonists

• peripherally selective µ-antagonists

length of postoperative ileus is

directly proportional to the administered amount of opioids

perioperatively

Cali et al., Dis Col Rec 2000; 43: 163

a selective peripheral µ-antagonist reduces postoperative ileus

*

020406080

100120

ADL 8-2698 vs. placebotime

to d

efec

atio

n (h

ours

)

ADL 8-2698

placebo

Taguchi et al., New Engl J Med 2001; 345: 935

* p< 0,05

NSAID

paracetamol

selective peripheralµ-opioid antagonists

postoperative analgesics and postoperative ileus

opioids

postoperative ileus

opioids

laparoscopic surgery

early feeding?NSAID

?

epidural local

anesthetics

laxatives?

prokinetic drugs

?

reducing postoperative ileusimplications for perioperative management

Kehlet, Br J Anaesth 1997; 78: 606

no GI tube

Basse et al., Ann Surg 2000; 232: 51Basse et al., Ugeskr Laeger 2001; 163: 913

accelerated programme - colonic surgerytime to postoperative defecation

2 2 10

20

40

60

1 2 3 4 5postoperative day

num

ber o

f pat

ient

s

n=100


0=day of surgery

median 1 day


accelerated programme - colonic surgerypostoperative hospital stay (incl. day of surgery)

0

20

40

60

2 3 4 5 6 7 9 11 62postoperative day of discharge

num

ber o

f pat

ient

s

n=100


median 2 days (48 hours)

length of postoperative ileus within a multimodal rehabilitation programme

n =3

9

n=10

0

n=22

n=22

n=31

0

1

2

3

Bardram (2000) Basse (2000/01) Smedh (2001) Senagore (2001) Basse (2002)

dura

tion

of P

I (da

ys)

Holte and Kehlet, Drugs 2002 (in press)

open colonic surgery

laparoscopic colonic surgery abdominal

rectopexy

laparoscopic colonic surgery

open colonic surgery

Basse et al., Br J Surg 2001; 88: 1998

conclusions on postoperative ileus

• multifactorial pathogenesis• postoperative epidural local anesthetics

most effective treatment• selective peripheral opioid-antagonists of

potential major importance in the future• postoperative ileus may be eliminated within

a multi-modal rehabilitation programme

postoperative ileus - pathophysiology and clinical implications

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