PERIOPERATIVE NUTRITIONAL

MANAGEMENT

Federico Bozzetti

Faculty of Medicine, University of Milan, Italy

TOPICS

● A historical perspective

● Lessons from RCT and meta-analyses

PN vs no specialised support (SS)

EN vs no specialised support (SS)

PN vs EN

IEEN vs EN

● The Milan experience

● Conclusions

TOPIC

● A historical perspective

● Lessons from RCT and meta-analyses

PN vs no specialised support (SS)

EN vs no specialised support (SS)

PN vs EN

IEEN vs EN

● The Milan experience

● Conclusions

A historical perspective

RATIONALE

• Malnutrition increases

postop complications

• Starvation of the gut

is deleterious

• Complications are

related to immune

suppression

CLINICAL APPROACH

• TPN in malnourished

pts (Holter&Fischer 1977)

• EN in surgical

patients (Bower et al 1986)

• Use of immune-

enriched EN formulae

(Daly et al 1992)

TOPIC

● A historical perspective

● Lessons from RCT and meta-analyses

PN vs no specialised support (SS)

EN vs no specialised support (SS)

PN vs EN

IEEN vs EN

● The Milan experience

● Conclusions

AUTHOR YEAR PREOPERATIVE POSTOPERATIVE

# n # n

Klein et al 1997 13 (1358) 9 (754)

Torosian 1999 14 (1245) 8 (710)

Braunschweig

et al 2001 2 (181)

Heyland et al 2001 11 (1165) 16 (1742)

Koretz et al 2001 25 (2164) 18 (482)

Preop PN vs no-SS (#:studies, n:patients)

Preop PN vs no-SS

Results from meta-analyses

• No reduction of mortality

• 4 out of 5 showed a decrease of serious complications from 40% (control) to 30% (PN)

• >5 days of preop PN necessary to get a benefit

• >7 days of preop PN necessary in severely malnourished patients

• Preop PN is indicated only in the 5% of elective surgical patients who are severely malnourished

Postop PN vs no-SS

• 9 studies (>700 patients, well and malnourished)

have compared PN to simple intravenous fluids

• 3 meta-analyses (Braunschweig et al 2001, Heyland et al 2001,

Koretz et al 2001)

• PN increased morbidity by 10%, mostly because

of septic complications

Preop standard EN vs no-SS

• Four RCT (Shukla 1988, Foschi 1986, Fynn&Leighhty 1987,

von Meyenfeldt 1992)

• Few studies because this approach

became quickly obsolete

• Reduction of surgical complications

Postop EN vs no-SS (from Koretz et al 2007)

• 13 RCTs, 1032 patients

• EN associated with fewer infections and a

tendency for fewer intra-abdominal or

intrathoracic complications

Postop early vs later EN ( from Lewis et al 2009)

• 13 RCTs (7 TF, 6 ONS) , 1173 patients

• Lower mortality and shorter length of

stayIncrease

• Increase of vomiting in EEN

PN vs EN

• 4 meta-analyses (Braunschweig et al 2001, Heyland et al

2001, Koretz et al 2001, Elia et al 2006)

• ~ 20 RCTs, ~1033 patients

• EN associated with fewer infections (RR

0.66), shorter hospital stay, no effect on

mortality

Postop PN vs EN

Meta-analysis of Mazaki and Ebisawa (2008)

(29 RCTs, 2552 patients)

EN beneficial in the reduction of

• any complication (RR 0.85)

• any infectious complication (RR 0.69)

• anastomotic leaks (RR 0.67)

• intrabdominal abscesses (RR 0.63)

• duration of hospital stay (RR -0.81)

IEEN vs EN (Marik and Zaloga 2010, Cerantola et al* 2010)

Meta-analysis* (21 RCTs, 2730 pts)

• IEEN; Arg, n-3FA, RNA (but 2 with Gln and n-3FA)

• Control: 9 isocal-isoN, 4 isocal

• Preop, postop, peri IEEN ↓ complications (OR: 0.48, 0.54, 0.39) ↓ infections (OR;0.36, 0.53, 0.41)

• IEEN reduced hospital stay by 2 days

• No difference in mortality

• 3 RCTs reported mean saving of 52%, 13% and 18%

TOPIC

● A historical perspective

● Lessons from RCT and meta-analyses

PN vs no specialised support (SS)

EN vs no specialised support (SS)

PN vs EN

IEEN vs EN

● The Milan experience

● Conclusions

The Milan experience

A wide literature supports the concept that

malnutrition adversely affects surgical outcome.

However, it is not clearly known whether a

perioperative nutritional support (and which one) has

a protective effect against complications when other

independent risk factors are accounted for.

AIMS OF THE STUDY

To investigate the potential joint prognostic role upon the

occurrence of postoperative complications in GI surgery for

cancer of:

• baseline demographic, clinical and nutritional parameters

• type of nutritional support

• intraoperative factors

PATIENTS & METHODS

We reanalysed databases of 1410 pts with GI cancer

included in 7 previous RCTs* on perioperative

nutritional support and receiving:

• standard intravenous fluid (SIF), n 149

• total parenteral nutrition (TPN), n 368

• enteral nutrition (EN), n 399

• immune-enhancing enteral nutrition (IEEN), n 500

* Gianotti (Arch Surg 1997), Braga (Arch Surg 1999), Bozzetti (JPEN 2000), Bozzetti (Lancet

2001), Braga (Crit Care Med 2001), Braga (Arch Surg 2002), Gianotti (Gastroenterology 2002)

NUTRITIONAL REGIMEN per day

• SIF 400 to 900 kcal

• TPN 25 to 34 kcal/kg + 0.25g N/kg

• EN,IEEN 25 to 28 kcal/kg + 0.25g N/kg

Definition of complications Wound infection Any redness/ tenderness of surgical wound with discharge of pus

Abdominal abscess Deep collection of pus

Pulmonary tract infection Abnormal chest X-ray with fever (>38° C) and WBC > 12.000 cells/mm3

and positive sputum or bronco-alveolar lavage.

Urinary tract infection More than 107 microorganisms per mL of urine

Bacteremia Two consecutive positive blood cultures without shock

Wound dehiscence Any dehiscence of the fascia longer than 3 cm.

Bleeding Necessity of blood transfusion ( 2 units)

Anastomotic leak Any dehiscence with clinical and radiologic evidence

Respiratory failure Presence of dyspnea and respiratory rate > 35/min or PaO2 < 70 mm Hg.

Circulatory insufficiency Unstable blood pressure requiring use of extra fluids and/or cardiac

stimulants

Renal dysfunction Increased serum urea and/or creatinine level (50% above baseline)

Renal failure Necessity of hemodialysis

Hepatic dysfunction Increased serum bilirubin level (50% above baseline)

Pancreatic fistula Daily output of fluid > 10 mL from surgical drainage with amylase level 5

times higher than serum concentration

Delayed gastric emptying Necessity of naso-gastric suction for more than 8 days after surgery

Multiple Organ Dysfunction

Syndrome (MODS)

A state of physiological derangement in which organ function is not

capable of maintaining homeostasis

MAJOR COMPLICATIONS

• lethal

• requiring relaparotomy

• requiring transfer to ICU

Statistical Methods

• Univariate analysis (Pearson’s 2 test)

• Multivariate analysis (logistic models)

Main series characteristics (1) SIF TPN EN IEEN TOT P

% % % % % §

Sex 0.161

Male 53.7 59.8 60.1 54.0 57.2

Age (years) 0.333

22.8 23.6 21.9 22.2 22.6

56-65 33.6 32.6 34.9 30.6 32.6

66-75 33.6 36.1 33.3 33.4 34.1

> 75 10.1 7.6 9.9 13.8 10.7

Tumor site <0.000

Colon-rectum 35.6 33.4 38.2 40.4 37.4

Stomach 45.6 46.2 42.0 36.4 41.5

Pancreas 18.8 20.4 19.8 23.2 21.1

Weight loss <0.000

10% 31.5 83.7 69.0 36.0 57.2

Duration of surgery

(hrs)

<0.000

20.8 15.2 6.8 7.6 10.7

2.1-5.0 66.4 67.8 73.4 70.8 72.7

> 5 12.8 17.0 19.8 21.6 19.0

Main series characteristics (2) SIF TPN EN IEEN TOT P

% % % % % §

Blood loss (mL) 0.274

> 500 26.0 36.7 34.6 34.6 34.4

Transfusions 0.109

Done 28.9 39.9 34.9 36.6 36.2

Haemoglobin (g/dL) 0.049

13.1 14.8 9.5 13.4 12.5

10.1-12.0 16.2 31.5 25.5 28.5 26.7

> 12.0 70.7 53.7 65.0 58.1 60.8

Lymphocytes

(x 1000/mmc)

17.2 26.1 23.5 25.9 23.8

1201-1500 22.8 30.3 30.1 20.1 25.1

> 1500 60.0 43.6 46.4 54.0 51.1

Albumin (g/dL) <0.000

3.4 20.3 15.6 4.5 10.4

3.1-3.5 24.0 32.8 32.1 19.5 26.2

> 3.5 72.6 46.9 52.3 76.0 63.4

0.016

RESULTS

COMPLICATIONS

• Minor 32%

• Major 7%

• Mortality 2.1%

Postoperative complications VARIABLE % pts with

complications

p

NUTRITION 0.000

SIF 50

TPN 43

EN 37

IEEN 33

AGE (yrs) 0.001

< 56 30

56-65 42

66-75 60

TUMOUR SITE <0.000

Colon-rectum 31

Stomach 40

Pancreas 51

WEIGHT LOSS <0.013

10% 42

< 10% 35

DURATION of SURGERY (hrs) 0.001

31

2.1-5.0 38

> 5.0 49

BLOOD LOSS (mL) 0.002

35

> 500 44

ALBUMIN (g/dL) 0.000

44

50

> 3.5 46

Postoperative infectious complications

VARIABLE %pts with

complications P

NUTRITION * 0.000

SIF 40

TPN 26

EN 20

IEEN 13

AGE (yrs) 0.046

< 56 17

56-65 20

66-75 21

< 75 28

TUMOUR SITE 0.011

Colon-rectum 17

Stomach 21

Pancreas 26

WEIGHT LOSS* 0.009

10% 23

< 10% 17

TRANSFUSIONS 0.040

yes 24

no 19

ALBUMIN (g/dL) 0.000

25

3.1-3.5 26

> 3.5 18

Multivariate analysis of risk factors for major complications OR P

§

Nutrition 0.002

TPN vs. SIF 0.39 0.19 - 0.80

EN vs. SIF 0.27 0.13 - 0.57

IEEN vs. SIF 0.32 0.16 - 0.63

Age (years) 0.050

56-65 vs. 55 1.48 0.72 - 3.05

66-75 vs. 55 1.55 0.77 - 3.12

> 75 vs. 55 3.05 1.35 - 6.86

Tumour site 0.004

Stomach vs. Colon-rectum 2.82 1.48 - 5.37

Pancreas vs. Colon-rectum 2.87 1.38 - 5.98

Weight loss ¶ -- 0.029

95% CI

--

§ Wald’s P for testing the overall association between the occurrence of complications

and main series characteristics

¶ OR and CI estimates are given only for categorical factors

Weight Loss (%)

0 5 10 15 20 25 30 35

Pro

bab

ility

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Standard

Parenteral

Enteral

Immune

Pro

ba

bilit

y o

f c

om

pli

ca

tio

ns

SIF

TPN

EN

IEEN

CONCLUSIONS (I)

● Preop (→postop)PN

- rarely recommended (only in elective surgery)

- useful in malnourished hospitalized pts,with non

working gut, fed >7days *

● Postop PN

- recommended in pts with complications, unable to

be fed enterally for at least 7 days *

* Grade A by the ESPEN GL 2009

CONCLUSIONS (II)

● Preop standard EN

- recommended in severely malnourished pts for 10-

14 d prior to major surgery *

● Postop (early) EN (TF or standard ONS)

- recommended after GI surgery *

● IEEN (preop, postop, peri) better than standard EN *

* GRADE A by ESPEN GL 2006

GRADE A by ESPEN GL

*

CONCLUSIONS (III)

Future challenges

• Gln-enriched solutions in malnourished patients

• Comparison/integration with preop CHO load

• Restrictive fluids

• Fast track/ERAS protocols

• Anti-ileus agents (lidocaine, methylnaltrexone,

alvimopan, laxatives, opioid-sparing analgesia….)

• Probiotics

• …………..

…knowledge is the enemy of

disease…