perioperative nutritional management · perioperative nutritional management federico bozzetti...
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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…