KAROLINSKA

INSTITUTET

Perioperativ Metabolism och Nutrition

Jonas Nygren, Kliniken för Kirurgi och Anestesi, Ersta Sjukhus

SwERAS-dagarna,

Stockholm, 21-22 November, 2019

Disclosures

None

The response to major surgery leads to morbidity

Metabolic homeostasis Inflammation, insulin resistance, catabolism

Fluid balance Hypoperfusion, overhydration, oedemia

Pain Somatic, visceral, neuropathic

Gut dysfunction Nausea, vomiting, paralysis

Cognitive dysfunction Delirium, confusion, sleep disruption

Post-operative deconditioning Immobilisation, fatigue, anemia, starvation It´s more to it than a perfect operation

Metabolic response to trauma

Neuroendocrine response

Cortisol, catecholamines, glucagon, GH

Insulin resistance

Catabolism

Lipolysis

Protein breakdown

Hyperglycemia

Inflammation

Cytokines

The Surgical Stress Response

Salt and water retention

Increased CO and O2 consumption

Mobilisation of energy reserves

Catabolism

Insulin resistance

Hyperglycemia

Surgical patients with low reserves are vulnerable

Malnutrition

Frailty

Sarcopenia

Gillis C, Anesthesiology, 2015

Mitochondrial

dysfunction

Energy production / oxidative phosphorylation / ATP

Decrerased fatty acid oxidation

Inhibiting insulin action / Insulin resistance

Toxic lipid metabolite accumulation

ROS production / oxidative stress

Uncoupling

Gonzalez-Franquesa A, Adv Exp Med Biol, 2017

Harmful positive feedback loop

Gonzalez-Franquesa A, Adv Exp Med Biol, 2017

Mitochondrial dysfunction and insulin resistance

Preoperative insulin resistance

increased risk for complications

The ORs were adjusted for potential confounders

Complication OR for every decrease by

1 mg/kg/min

(Insulin sensitivity)

P

value

Death 2.33 (0.94-5.78) 0.067

Major complication 2.23 (1.30-3.85) 0.004

Severe infection 4.98 (1.48-16.8) 0.010

Minor infection 1.97 (1.27-3.06) 0.003

Sato et al, JCEM 2010; 95: 4338-44

273 patients open cardiac surgery, insulin sensitivity determined at the end of op

Controlling perioperative physiologyMany small pieces of the puzzle

Gillis C

, Anesth

esiolo

gy, 2

015

ERAS

Regional

analgesia

Prevention

of ileus/

prokinetics

CHO -loading/

no fasting

Early

mobilisation

Periop fluid

management

DVT

prophylaxis

Preopcouncelling

Avoiding opioids

No premedication

No oral bowel prep

Perioperative

Nutrition

Active warming

Oral analgesics/

NSAID’s

Incisions

No NG tubes

Early removal

of catheters/drains

LOS

Compl

Lap CRC surgery

ERAS vs Trad

Meta-analysis

13 RCT, n=1298

• Shorter LOS

• Reduced

complications

• Faster return

• bowel function

• Less SIRS• CRP

• IL6

Ni X, J Gastrointest Surg, 2019

*

*

*

*

*

ERAS

Lap Colonic resection

• n=48

• 2 Complications

• 1 Readmission

Patel G, Am J Surg, 2010, Levy BF, Dis Col Rect, 2009

Gillis C

, Anesth

esiolo

gy, 2

01

5*

*

*

*

Summary

Major surgery

significant morbidity and surgical stress

ERAS are evidence based perioperative protocols

reduces surgical stress

improves postoperative outcome

ERAS

Epidural

Anaesthesia

Prevention

of ileus/

prokinetics

CHO - loading/

no fasting

Early

mobilisation

Peri-op fluid

management

DVT

prophylaxis

Pre-op councelling

Remifentanyl

No - premed

No bowel prep

Perioperative

Nutrition

Bairhugger

Oral analgesics/

NSAID’s

Incisions

No NG tubes

Early removal

of catheters/drains

Malnutrition

Nearly 50% of patients admitted to hospital

Increased mortality and morbidity

Longer hospital stay and increased costs

Meta analysis 15 RCTs n= 3831, 2015

Cochrane review, GI surgery, 13 RCTs, n= 548, 2012

Obstruction

Malabsorbtion

Drug / Treatment related side effects

Metabolic abnormalities

Patient related factors

After surgery Organisational barriers in hospital

Missed meals etc

Pre‐operative nutrition and the elective surgical patient: why, how and what?

Anaesthesia, Volume: 74, Issue: S1, Pages: 27-35, First published: 02 January 2019, DOI: (10.1111/anae.14506)

ERAS Guidelines / Nutrition

ColoRectal surgery Patients should be screened for nutritional status

If deemed to be at risk of under-nutrition, they should be given active nutritional support.

Preoperative fasting should be minimised.

Patients should be encouraged to take normal food as soon as possible after surgery.

ONS can be used to supplement total intake.

Gustafsson, ClinNutr, 2012

Preoperative optimisationPrepare before surgical stress

Cardiopulmonary function

Anemia

Glucose / Diabetes control (HbA1C < 7.5)

Smoking cessation

Alcohol abstinence

Physical function / exercise

Nutritional state

Weight loss

Morbid obesity

Electrolytes / Trace elements

Fluid homeostasis / Dehydration

PR

EH

AB

ILIT

AT

ION

Preoperative weight lossAdverse postoperative outcome

Studley, JAMA, 1936, Meguid, Am J Surg, 1988

Weight loss Mortality

<20% 3.5 %

>20% 33 %

Current practice

132 patients in Manchester, UK

resectable CRC, 2-4 weeks preoperatively

50 % weight losing

20% malnourished

173 departments in Swiss and Austria

80% aware of reduced complications / reduced LOS

Only 20 % had nutritional screening

Only 14% used a nutrition score

Grass et al, Eur J Clin Nutr. 2011, Burden, J HND, 2010

Detect and Correct to Protect

Screening

Assessment

Nutrition care plan

Preoperatively

Avoid preoperative fasting

Postoperatively

After discharge

In malignant disease, interventions need to be initiated immediately at outpatient clinic

Nutritional screening

SGA Medical-surgical hospitalized and outpatients

NRS-2002 Medical-surgical and acute hospitalized

MNA-SF Ambulatory and subacute

MST Acute hospitalized and oncology outpatients

MUST Medical and surgical hospitalized

NST/BAPEN Acute hospitalized

Simple, 2-part Acute hospitalized

NRS Acute care, medical and surgical

Screen-II/AB Seniors in the community/geriatric clinics

Rapid screen Subacute care (rehabilitation center)

Tool #1 Elderly in acute care and long-term care

SNAQ V Not evaluated against a reliable standard

Subjective Global Assessment - SGA

Weight loss

over 6 months

in past 2 weeks

Dietary intake

GI symptoms

• Functional status

• Disease state and co-morbidity

• Loss of fat

• Muscle wasting

• Edema

• Ascites

Signs of malnutrition

Loss of muscle

Loss of fat

Nails

Hair

Mouth

Teeth

Edema

Ascites

Loss of function

Lethargy (Depression)

Muscle wasting in obese may be difficult to determine

Nutritional assessment

History Diet and weight loss

Physical examination BMI

Tissue stores of muscle and fat

Mid arm circumference and triceps skin fold

Grip strength and FEV

BIA and DEXA and indirect calorimetry

CT scan

Lab Albumin and pre-albumin

Transferrin and retinol-binding protein

Postoperatively these proteins are markers for surgical stress

Preoperative assessment

Current nutritional status

Starvation (anorexia, stricture)

Chronic disease

Acute disease

Severity of the surgical insult

Procedures with high infection rates and long hospital

stay

Malnutrition using SGA screening

and postoperative outcome

Baker NEJM, 1982, Machija, NCP 2008

0

10

20

30

40

50

60

70

80

Infections (%) LOS (days)

SGA A

SGA B

SGA C

P<0.005 (infections)

P<0.0001 (LOS)

Historical data on preoperative TPN

TPN (c:a 2500 kcal, 80 g protein/d) 5-10 d before

major surgery reduce complications

Klein S, JPEN 1997

0

5

10

15

20

25

30

35

40

45C

om

pli

cati

on

s (

%)

Control

TPN

Systematic review of 13 studies in mostly malnourished patients

Expert committee supported by NIH, ASPEN and ASCN

Nutrition before GI surgery

Immune-enhancing nutrition before GI surgery (7 RCT. N=548) Mostly well-nourished patients

5-7 days before surgery

Additional Arginine, Omega 3, (RNA), (Glutamin)

Reduced total complications

Reduced infectious complications

Reduced hospital stay

Preoperative PN (3 RCT)

Mostly malnourished

10 days before surgery

Reduced major complications

No difference in infectious complications

Oral (3 RCT) or Enteral(2 RTC) standard nutrition

vs no nutrition

No effect on outcomes

Preoperative nutrition

Need to be evaluated in conjunction with ERAS protocols

Burd

en. C

och

rane

revi

ew, 2012

ERAS / ESSO guidelines

Position paper

Nice short review

Sandrucci S, EJSO, 2018

Nutritional support

RCT, CRS, n=101

Weight losing patients > 1kg /6 months

250 ml ONS for 8 (5-15) days preop

vs dietary advice alone

Less weight loss postop (7 vs 10 %)

Fewer infections (30 vs 47%)

Burden S, J Cach Sarc Muscle, 2017

*

ImmunonutritionNutrients, which influence immunity

Omega-3 polyunsaturated fatty acids

Inhibits inflammation, enhances T cell functions

Changes in membrane phospholipids

Changes in cytokine and lipid-derived mediator production

Arginine

Enhances T cell function

Stimulation of growth hormone production

Altered nitric oxide production?

Glutamine

Stimulates T cell function, inhibits inflammation?

Stimulation of glutethione synthesis?

Enhances cell proliferation, increases

Sulphur amino acids and related compounds

Inhibits inflammation enhances T cell function

Suppression of oxidant effects and NFkB activation

Maintenance of glutathione status

Fig. 1

European e-Journal of Clinical Nutrition and Metabolism 2009 4, e10-e13DOI: (10.1016/j.eclnm.2008.07.015)

Immuno-enhancing nutrition before GI surgery

Total complications

IE vs no nutrition

Burden. Cochrane review, 2012

IE vs standard nutrition

Immunonutrition in cancer surgery• 61 RCTs, n=5000, mostly GI

• Reduced infectious complications

• Reduced anastomotic leak

• Reduced LOS

Yu K, JPEN, 2019

Criticism Immunonutrition literature

Recent meta analysis in BJS (83 RCTs, n=7116) Overall

Reduced total (OR 0,79) and infectious complications (OR 0,58)

Reduced Shorter LOS (-1,79 days)

Little evidence from studies in

Minimally invasive surgery

ERAS

Bias

Reporting bias

Publication bias

Industry bias

When studies with high or unclear risk of

bias was excluded;

evidence was substantially lowered Probst P, BJS, 2017

Immunonutrition in ERAS

264 pat undergoing colorectal resection in ERAS

Randomised to Immunonutrition 400 ml

7 days before and 5 days after surgery

Standard nutrition 400 ml

In addition to normal food ad lib

Reduced Total complications (35 vs 23%)

Infections complications (24 vs 11%)

Wound infections (16 vs 6 %)

Moya P, Medicine, 2016

Preoperative Nutrition Recommendations

•Screen all patients undergoing major GI surgery

•If malnourished (SGA B och C)

•Provide oral supplements

•In case of a stricturing process or GI tolerance

•ONS covering energy and protein requirements

•Sometimes residue low diet, if possible

•Consider parenteral nutrition

•Tailored nutrition depending on GI tolerance

Summary

Preoperative Nutrition

Malnutrition is related to adverse outcome

Current practice rarely include

Nutritional screening

Nutritional intervention

Even brief nutritional intervention improve outcomes

All malnourished patients before any procedure

Consider all patients before major surgery (IE)

Summary Nutritional support

Nutritional supplements

More energy

More protein

1.2-2 g/ kg/ 24h in surgical patients

Immunonutrition

Vitamin D

Omega 3 FFA

Exercise

Improves anabolic effect from feeding

20 g protein maximally stimulates protein synthesis

Postoperative nutrition

Early enteral nutrition improves clinical outcome

Lewis BMJ 2001, Lewis, JGS, 2009

Updated meta-analysis 2009 show reduced mortality in early feeding 2.4 % vs 6.9%

Oral energy intake after major open

colorectal surgery in ERASNot a big problem

0

500

1000

1500

2000

0 1 2 3 4 5 6 7

Postop days

Kc

al /

24

h

N=143

Data from Ersta Hospital

Oral supplements in addition to a normal diet

Henriksen Nutrition 2002

Postoperative nutrition

1340 Kcal

in a 70 kg person

Fascilitate nutrition

Avoid fasting Preoperative carbohydrate loading

Enhance nutritient utilization Epidural analgesia

Optimize fluid dynamics

Control PONV Multimodal analgesia

Fascilitate mobilization

Chewing gum

Coffee

Prokinetics (Prucalopride)

Early NG in case of gastric retention !!

Stoma tubing

Avoid aspirationGianotti L, Clin Nutr, 2019

Day of surgery Free oral intake

≥600 kcal ONS /24h

Postoperatively ≥900 kcal ONS / 24h

Post discharge ONS if inadequate food intake or preoperative malnutrition

Postoperative Nutrition Recommendations

Parenteral nutrition:

Well fed INFECTIONS

Malnutrition Mortality

Postoperative nutrition

Braunschweig Am J Clin Nutr 2001

Parenteral Nutrition in reduced GI tolerance

ALWAYS TRY ORAL or ENTERAL ROUTE FIRST !

SGA A PN after 5 days with a low energy intake

(<800 kcal/24h)

SGA B-C PN after 2 days with a low energy intake

(<800 kcal/24h)

Postoperative Nutrition Recommendation

Infectious complications

Fish oil based postoperative PN, 21 RCTs

Li, Clin Nutr, 2014

Length of stay

Fish oil based postoperative PN, 21 RCTs

Li, Clin Nutr, 2014

Post-discharge nutrition

No evidence for improved clinical outcome

1-4 months treatment with ONS

4 RCTs

Lack of robust data

Lidder, NCP, 2009

Conclusion

Nutritional screening

Nutritional intervention In malnutrition, 7-14 days of preoperative nutrition

Consider Immune-enhancing nutrition for 5-7 days

before major surgery

Postoperative multimodal ERAS interventions Early oral feeding

Enhancing GI recovery

Consider ONS or Immune-enhancing nutrition

Studies on nutritional interventions in ERAS surgery is needed

KAROLINSKA

INSTITUTET

KAROLINSKA

INSTITUTETIt´s more to it than a perfect operation

ONS preoperatively

RCT, CRS, n=125

400 ml ONS >10 days

Including well-nourished pats No effect

RCT, CRS, n=179 ONS ad lib, mean 15 days (7-61)

Including well-nourished pats

Less weight loss, less minor complications

RCT, CRS, n=101

Weight losing patients > 1kg /6 months

250 ml ONS for 8 (5-15) days preop

vs dietary advice alone

Less weight loss postop (7 vs 10 %)

Fewer infections (30 vs 47%)

Burden S, J Cach Sarc Muscle, 2017, Burden S, J Hum Nutr Diet 2011, Smedley, BJS, 2004

*

Gillis C, Anesthesiology, 2015

Permissive underfeeding ?

Meta analysis on 12 studies (8 RCT)

Short term nutritional support

>50% but less than 100 % of energy requirements

Improved outcomes

Reduced morbidity

From short term underfeeding

However, poor study design and heterogeneity common

Owais, APT, 2010

LAFA trial, n=79Veenhof A, Ann Surg, 2012

LS Lap Standard

LFT Lap FT

OS Open Standard

OFT Open FT

HLA-DR

CRP IL6

Refeeding syndromecan be fatal

Hypophosphatemia

Hypokalemia

Hypomagnesemia

Volume overload

Cardiopulmonary

Neurologic

Hematologic

Increased BMR

ATP depletion

Provide only 50-70% of energy intake normally required first 3-5 days in severe cases

Monitor electrolytes

Tiamin. vitamins

Pro-kinetics and PPI to support enteral/oral route

Gillis C, Anesthesiology, 2015