Pathophysiological stress response following surgery & ERAS · Pathophysiological stress response...
Transcript of Pathophysiological stress response following surgery & ERAS · Pathophysiological stress response...
Pathophysiological stress responsefollowing surgery & ERAS
Olle Ljungqvist MD PhDProfessor of Surgery Örebro University & Karolinska Intitutet Stockholm Sweden
Chairman ERAS Society
ERAS UK conference 2013
Birmingham November 8 2013
Recovery After SurgeryWhat are we trying to achieve?
Patient back to preoperative function
• Normal gastrointestinal function
– Normal food intake
– Bowel movement
• Pain control
• Mobility
• No complication
The Metabolic Stress Response to
Surgery and Trauma
Philosophy
ERAS philosophy: The Patients journey
PreopSurgery
Anesthesia
Recovery
Ward
Audit compliance & outcomes
Home
H
D
U
C
l
i
n
i
c
Audit compliance and outcomePatients journey
ERAS
Epidural
Anaesthesia
Prevention
of ileus/
prokinetics
CHO - loading/
no fasting
Early
mobilisation
Peri-op fluid
management
DVT
prophylaxis
Pre-op councelling
Short acting anestetics
No - premed
No bowel prep
Perioperative
Nutrition
Body heating devises
Oral analgesics/
NSAID’s
Incisions
No NG tubes
Early removal
of catheters/drains
Fearon et al, Clin Nutr 2005
ERASSecuring modern care
Surgeon:
No bowel prep
Food after surgery
No drains
Early removal u-catheter
No iv fluids, no lines
Early discharge
All evidence based!
Anesthetist:
Carbohydrates no fasting
No premedication
Thoracic Epidural Anesthesia (open)
Balanced fluids
Vasopressors
No or short actingopioids
ERAS team approach
• Surgeon
• Anesthestist
• HDU specialist
• Ward nurses
• Anesthesia nurses
• Physiotherapist
• Dietitian
• Management
Team work:
• Training
• Implementing
• Planning
• Auditing
• Updating
• Reporting
• Research
ERAS works!
ERAS Meta analys
ERAS: shorter length of stay by 2.5 days
Varadhan et al, Clin Nutr 2010
ERAS Meta analys
ERAS: Reduce complications by 50%
Varadhan et al, Clin Nutr 2010
How does ERAS work?
Mechanisms
3 new guidelines 2012
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
Fearon et a al 2005, Lassen et al Arch Surg 2009
How does ERAS work?
Mechanisms
Insulin
Insulin & Recovery
Insulin: main anabolic hormone involved in• All parts of metabolism
– Glucose control– Fat metabolism– Protein
• Regulator of return of key functions• Central to development of complications• Affected by many perioperative treatments
Insulin & Recovery
Insulin: main anabolic hormone involved in• All parts of metabolism
– Glucose control– Fat metabolism– Protein
• Regulator of return of key functions• Central to development of complications• Affected by many perioperative treatments
• Insulin resistance: a key for understanding and enhancing recovery
Postoperative Insulin resistance
Defintion:
Below normal metabolic effect of insulin
• Glucose uptake
• Reduction in glucose production
• Lipolysis
• Protein breakdown / balance
Insulin sensitivity falls with the magnitude of surgery
Adopted from Thorell et al: Curr Opin Clin Nutr Metab Care 1999
-80
-70
-60
-50
-40
-30
-20
-10
0
Lap chol Open hernia Open chol Open colorectal
Reduction in Insulin Sensitivity (%)
Post
op
/ P
reo
pM
-val
ue
x 1
00
(%
)
P < 0.001, ANOVAn = 6-13
MoreInsulin
Resistance
Preop level
Independent factors predicting length of stay
• Type of surgery
• Perioperative blood loss
• Postoperative insulin resistance
R2 = 0.71, p < 0.01
Thorell et al: Curr Opin Clin Nutr Metab Care 1999
Muscle
Fat
Liver
Kidney
Blood cells
Endothel
Storage
Neural tissue
Insulin regulatedConcentration regulated
Fat
[B-Glucose]
Glucose uptake
Muscle
Fat
Liver
Kidney
Blood cells
EndothelNeural tissue
Insulin regulatedConcentration regulated
Glucose uptake- meal
Fat
Liver
Kidney
Blood cells
Endothel
Storage
Neural tissue
Insulin regulatedConcentration regulated
[B-Glucose]
Glucose uptake- stress
Fat
Liver
Kidney
Blood cells
Endothel
Neural tissue
Insulin regulated
Concentration regulated
[Glucose]Muscle
Driving forces for hyperglycemiaafter surgery
Postop
Hyperglycemia +
Insulin sensitivity -
Glucose production +
Peripheral glucose uptake -
GLUT4 translocation -
Glycogen formation -
Adopted from Ljungqvist et al, Clin Nutr 2001
Postop Type 2 DM
Hyperglycemia + +
Insulin sensitivity - -
Glucose production + +
Peripheral glucose uptake - -
GLUT4 translocation - -
Glycogen formation - -
Adopted from Ljungqvist et al, Clin Nutr 2001
Driving forces for hyperglycemiaafter surgery similar to diabetes
Normalizing insulin action normalizes metabolism
Insulin infusion to normalize:
• Blood glucose
Also controlled:
• FFA
• Urea excretion
• Substrate utilization after major surgery
Insulin resistance the key to catabolism
Brandi LS et al: Clin Sci 1990
Glucose uptake- stress
Fat
Liver
Kidney
Blood cells
Endothel
Neural tissue
Insulin regulated
Concentration regulated
[Glucose]Muscle
Too little
Too much
Insulin resistance muscle
• Reduced glucose uptake
• Reduced glycogen storage
• Increased protein catabolism
Insulin resistance muscle
• Reduced glucose uptake
• Reduced glycogen storage
• Increased protein catabolism
Lean body massLean body mass
Muscle functionMuscle function
MobilisationMobilisation
Energy supplyEnergy supply
Impaired Recovery
Postop (days) Tissues/cells
Muscle weakness muscle
Infections leukocytes
Cardiovascular blood vessels
Renal failure kidney
Polyneuropathy nerve tissue
Glucose uptake- stress
Fat
Liver
Kidney
Blood cells
Endothel
Neural tissue
Insulin regulated
Concentration regulated
[Glucose]Muscle
Too little
Too much
Complications
Postop (days) Tissues/cells
Infections leukocytes
Cardiovascular blood vessels
Renal failure kidney
Polyneuropathy nerve tissue
Muscle weakness muscle
Why these organs/cells?
Tissues unprotected to glucose uptake:
• Uncontrolled inflow of glucose• No storage• Overflow of glycolysis• ROS production• Block of glycolysis & Krebs cycle• Altered gene expression• Enhanced inflammatory response• Vicious circle
Vicious circle
ROS production
Enhanced inflammation Insulin resistance
Hyperglycemia
Stress of surgery
Stress hormones Cytokines
Insulin important for wound healing
• 6 patients studied twice, >40% burn injury
• Placebo – randomised - cross over design
• Hyperinsulinemia
– 400-900 microunits/ml for 7 days or placebo
• Glucose infusion to normoglycemia
• Donor-site healing time reduced
– from 6.5 to 4.7 days, p < 0.05
EJ Pierre et al, J Trauma 1998
Glucose levels in ERAS& outcomes after surgery
• 120 Consecutive patients
• Colorectal surgery
• No history of diabetes
• Preop HbA1c – above or below 6.1
• 26% pathologically high (≥ 6.1 mM)
• Glucose 5 times daily postop
• CRP and complications (30 day follow up)
Gustafsson et al, BJS 2009: 96; 1358-64
Gustafsson et al, BJS 2009: 96; 1358-64
Glucose after major elective surgery
N = 1201500 kcal/d
0
20
40
60
80
100
120
1
CR
P m
g/L
HbA1c < 6.1
HbA1c ≥ 6.1
*
* P< 0.05
CRP postop day 1
Gustafsson et al, BJS 2009: 96; 1358-64
HbA1c, Glucose controland postop complications
Gustafsson et al, BJS 2009: 96; 1358-64
0
5
10
15
20
25
30
35
40
45
50
Complications infections
HBA1c >6.1
HBA1c ≤6.1
OR 2.9P < 0.05
OR 2.3P=0.13
% o
f p
atie
nts
Postoperative insulin resistanceincrease the risk for complications
The ORs were adjusted for potential confounders
Complication OR for every decrease by1 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
ERAS
EpiduralAnaesthesia
Preventionof ileus/
prokinetics
Preop CHO/no fasting
Early mobilisation
Peri-op fluidbalance
DVT prophylaxis
Pre-op councelling
Short acting anaesthetics
No - premed
No bowel prep
Early postoporal feeding
Maintaining body temperature
Oral analgesics/NSAID’s
Surgicaltechnique
No NG tubes
Early removalof catheters/drains
Fearon et al, Clin Nutr, 2005
ERAS
EpiduralAnaesthesia
Preventionof ileus/
prokinetics
Preop CHO/no fasting
Early mobilisation
Peri-op fluidbalance
DVT prophylaxis
Pre-op councelling
Short acting anaesthetics
No - premed
No bowel prep
Early postoporal feeding
Maintaining body temperature
Oral analgesics/NSAID’s
Surgicaltechnique
No NG tubes
Early removalof catheters/drains
Fearon et al, Clin Nutr, 2005
ERAS elements to reduce insulin resistance
Preoperative
• Preoperative carbohydrates
• Epidural anesthesia
Postoperative
• Pain control
• Early postop feeding
Preoperative CHO reducespostop insulin resistance
-60
-50
-40
-30
-20
-10
0
10
20
Cholecystectomy Colorectal Arthroplasty Arthroplasty
* * * *
*P < 0.05
Nygren et al: Curr Opin Clin Nutr Metab Care 2001
CHOControl
More resistance
Preoperative carbohydrates retains lean body mass (MAC)
Yuill et al, Clin Nutr 2005
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
CHO
Placebo
P <0.05
[cm]
0
1
2
3
4
5
6
Ure
a lo
sse
s (m
mo
l/kg
/d)
Preoperative carbohydrates reduces protein losses and improves muscle
strength
P<0.05
-16
-14
-12
-10
-8
-6
-4
-2
0
Po
sto
pe
rati
ve m
usc
le s
tre
ngt
h (
%)
ControlCHO
P<0.05
Mean (SEM)
Crowe, BJS 1984; Henriksen Acta Anaesth Scand 2003
Urea losses Muscle strength
EDA reduces postoperative insulin resistance
Uchida, Br J Surg 1988
-100
-50
0
50
100
150
200
250
300
350
Epinephrine Cortisol Insulin sensitivity
Po
sto
per
ativ
e c
han
ge (
%)
IV Opiates EDA *p<0.05**p<0.01
* * **
EDA + Preoperative CHO to control glucose during enteral feeding
Soop M et al, Br J Surg, 2004; *Harrison et al, JPEN 1997
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Glu
co
se
(m
mo
l/l)
Day
complete
hypocaloric
Traditional*
No insulin required
Insulin sensitivity improved with pre op Carb, EDA + post op feed
From Thorell et al: Curr Opin Clin Nutr Metab Care 1999, Soop M et al, Br J Surg, 2004
-80
-70
-60
-50
-40
-30
-20
-10
0
Lap chol Open hernia Open chol Open colorectal
Post op change in Insulin Sensitivity (%)
Post
op
/ P
reo
pM
-val
ue
x 1
00
(%
)
MoreInsulin
Resistance
Preop level
CHOEDAPostop
Feed
CHOEDAPostop
Feed
EDA vs. Iv opiates
Jorgensen Cochr Database Syst Rev 2004
Epidural - less paralysis
ERAS: oral intake development (mean
intake postop day 1-4)
Insulin sensitivityDay before surgery
Insu
lin s
en
sitv
ity
Bowel prepNo nutrition
Dinner, normal sleep
ERAS Care
Traditional care
Insulin sensitivityMorning of surgery
Insu
lin s
en
sitv
ity
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
ERAS Care
Traditional care
Insulin sensitivityMorning of surgery
Insu
lin s
en
sitv
ity
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
ERAS Care
Traditional care
Insulin sensitivityAnesthesia start
Insu
lin s
en
sitv
ity
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
Thoracic Epidural
Preoperative sedation
ERAS Care
Traditional care
Insulin sensitivityReaction to surgery
Insu
lin s
en
sitv
ity
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
Thoracic Epidural
Preoperative sedation
Surgery
Greater drop without Epidural
ERAS Care
Traditional care
Insulin sensitivityAfternoon of surgeryIn
sulin
se
nsi
tvit
y
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
Thoracic Epidural
Preoperative sedation
Surgery
Immediate feeding & mobilisation
NPO iv low caloric fluids
ERAS Care
Traditional care
Insulin sensitivityDays after surgery
Insu
lin s
en
sitv
ity
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
Thoracic Epidural
Preoperative sedation
Surgery
Immediate feeding & mobilisation
NPO iv low caloric fluids
Oral feeding & mobilisation
Slow return to feeding and mobilisation
Days - weeks
ERAS Care
Traditional care
Insulin sensitivity Days after surgery
Ins
uli
n s
en
sit
vit
y
Bowel prepNo nutrition
Dinner, normal sleep
Carbohydrate treatment
Overnight fasting
Thoracic Epidural
Preoperative sedation
Surgery
Immediate feeding & mobilisation
NPO iv low caloric fluids
Oral feeding & mobilisation
Slow return to feeding and mobilisation
Days - weeks
ERAS Care
Traditional care
Ljungqvist JPEN 2012
-80
-60
-40
-20
0
20
40
60
80
100
N losses N balance Energyexp
Glucose Insulin Insulinsens
Post
op
erat
ive
chan
ge (
%)
Traditional
Metabolic response to surgery intraditional perioperative care
-80
-60
-40
-20
0
20
40
60
80
100
N losses N balance Energyexp
Glucose Insulin Insulin
sens
Post
op
erat
ive
chan
ge (
%)
Traditional ERAS protocols
Metabolic response to surgery in traditional perioperative care vs. ERAS
protocols
Conclusions
• Minimizing metabolic stress is key to improved recovery
• Insulin resistance is central
• ERAS principles works in all major surgery
• Many ERAS components reduce metabolic stress
• Combining ERAS elements for best results
2013-11-12 63
• Valencia Spain
• April 23-26, 2014
• Multiprofessional
• Multi disciplinary
• Patient, Practice & Outcomes
• Henrik Kehlet Lecture:– Economics of ERAS / A Senagore
• ERAS Lecture:– Postoperative cognition / S Newman
• World leaders in ERAS
2nd World ERAS Congress