Guidelines for Perioperative Care for Pancreaticoduodenectomy: [622852]

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Guidelines for Perioperative Care for Pancreaticoduodenectomy: [622852]

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Guidelines for Perioperative Care for Pancreaticoduodenectomy:
Enhanced Recovery After Surgery (ERAS/C210) Society
Recommendations
Kristoffer Lassen •Marielle M. E. Coolsen •Karem Slim •Francesco Carli •
Jose´E. de Aguilar-Nascimento •Markus Scha ¨fer •Rowan W. Parks •
Kenneth C. H. Fearon •Dileep N. Lobo •Nicolas Demartines •Marco Braga •
Olle Ljungqvist •Cornelis H. C. Dejong
/C211Socie´te´Internationale de Chirurgie 2012
Abstract
Background Protocols for enhanced recovery provide com-
prehensive and evidence-based guidelines for best periopera-
tive care. Protocol implement ation may reduce complication
rates and enhance func tional recovery and, as a result of this,
also reduce length-of-stay in hospital. There is no compre-
hensive framework available for pancreaticoduodenectomy.
Methods An international working group constructed within
the Enhanced Recovery After Surgery (ERAS/C210) Society
constructed a comprehensive and evidence-based framework
for best perioperative care for pancreaticoduodenectomypatients. Data were retrieved from standard databases and
personal archives. Evidence and recommendations were
classiﬁed according to the GRADE system and reachedthrough consensus in the group. The quality of evidence was
rated ‘‘high’’, ‘‘moderate’’, ‘‘low’’ or ‘‘very low’’. Recom-
mendations were graded as ‘ ‘strong’ ’ or ‘ ‘weak’ ’.Results Comprehensive guidelines are presented. Avail-
able evidence is summarised and recommendations given for
27 care items. The quality of evidence varies substantiallyand further research is needed for many issues to improve the
strength of evidence and grade of recommendations.
Conclusions The present evidence-based guidelines pro-
vide the necessary platform upon which to base a uniﬁed
protocol for perioperative care for pancreaticoduodenec-
tomy. A uniﬁed protocol allows for comparison betweencentres and across national borders. It facilitates multi-
institutional prospective cohort registries and adequately
powered randomised trials.
Introduction
Enhanced Recovery After Surgery (ERAS), Fast-Track or
Clinical Pathway programmes are multimodal strategies thatThis work was conducted on behalf of ERAS/C210Society, the European
Society for Clinical Nutrition and Metabolism and the International
Association for Surgical Metabolism and Nutrition.
The guidelines are published as a joint effort between the Enhanced
Recovery After Surgery (ERAS) Society, for Perioperative Care, The
European Society for Clinical Nutrition and Metabolism (ESPEN) and
The International Association for Surgical Metabolism and Nutrition(IASMEN) and copyrights for this publication is shared between thethree societies. The guidelines are published jointly in World Journal of
Surgery (IASMEN) and Clinical Nutrition (ESPEN), and will also be
available on the ESPEN ( http://www.espen.org ) and ERAS Society
website ( http://www.erassociety.org ).
K. Lassen ( &)
Department of GI and HPB Surgery, University Hospital
Northern Norway, Tromsø and Institute of Clinical Medicine,
University of Tromsø, Tromso ¨, Norway
e-mail: [anonimizat]; [anonimizat]
K. Lassen /C1R. W. Parks /C1K. C. H. Fearon
Clinical Surgery, University of Edinburgh, Royal Inﬁrmary
of Edinburgh, Edinburgh, United Kingdom
M. M. E. Coolsen /C1C. H. C. Dejong
Department of Surgery, University Hospital Maastricht and
NUTRIM School for Nutrition, Toxicology and Metabolism,
Maastricht, The NetherlandsK. Slim
Department of Digestive Surgery, Hospital CHU Estaing,
Clermont-Ferrand, France
F. Carli
Department of Anesthesia, McGill University Health Centre,
Montreal, QC, Canada
J. E. de Aguilar-Nascimento
Department of Surgery, Federal University of Mato Grosso,
Cuiaba, Brazil
123World J Surg (2013) 37:240–258
DOI 10.1007/s00268-012-1771-1

aim to attenuate the loss of, and improve the restoration of,
functional capacity after surgery. Morbidity is reduced [ 1]
and recovery enhanced by reducing surgical stress, by opti-
mal control of pain, early oral diet and early mobilisation. Asa consequence, length-of-stay in hospital (LOSH) and costs
are also reduced. The ERAS group has published evidence-
based consensus recommendations for colorectal surgery[2,3]. Beneﬁcial experiences with clinical pathway pro-
grammes after pancreaticoduodenectomy (PD, Whipple’s
procedure) have been published [ 4–9], but the reported series
employed different protocols, or no prospective protocol at
all [6]. A comprehensive consensus framework is presented
on which to base a future protocol for optimal perioperative
care after PD. Such a recommendation will allow for a uni-
ﬁed protocol to be developed and validated prospectivelyacross different institutions and healthcare systems. This
guideline framework has been formulated and endorsed by
the ERAS Society, European Society for Clinical Nutritionand Metabolism (ESPEN) and the International Association
for Surgical Metabolism and Nutrition (IASMEN).
Methods
Literature search
The authors met in April 2011 and the topics to be included
were agreed and allocated. A principal literature search up
to June 2011 was undertaken. Comprehensive drafts were
circulated for discussion and reviewed in a group confer-ence in November 2011. Additional relevant literature
published after June 2011 was considered by members of
the group at meetings in November 2011 and May 2012.
Study selection
All co-authors screened web-based databases and personal
archives for relevant articles. Non-systematic emphasis was
given to more recent publications and publications of betterquality (moderate- and high-quality randomised controlled
trials and high-quality, large cohort studies; and systematic
reviews and meta-analyses of these). Retrospective series wereconsidered only if data of better quality could not be identiﬁed.Quality assessment and grading
The strength of evidence and conclusive recommendations
were assessed and agreed by all authors in May 2012.
Quality of evidence and recommendations were evaluatedaccording to the Grading of Recommendations, Assess-
ment, Development and Evaluation (GRADE) system [ 10–
12]. Quoting from the GRADE guidelines [ 12], the rec-
ommendations are: ‘‘Strong recommendations indicate that
the panel is conﬁdent that the desirable effects of adherence
to a recommendation outweigh the undesirable effects’’.‘‘Weak recommendations indicate that the desirable effects
of adherence to a recommendation probably outweigh the
undesirable effects, but the panel is less conﬁdent’’. Rec-ommendations are based on quality of evidence (high,
moderate, low, very low) but also on the balance between
desirable and undesirable effects; and on values and pref-erences [ 12]. The latter implies that, in some cases, strong
recommendations may be reached from low-quality data
and vice versa. A summary of the guidelines is shown inTable 1.
Evidence and recommendations
Preoperative counsellingPreoperative counselling targeting expectations about sur-
gical and anaesthetic procedures may diminish fear andanxiety and enhance postoperative recovery and discharge
[13–15]. Personal counselling, leaﬂets or multimedia
information containing explanations of the procedure alongwith tasks that the patient should be encouraged to fulﬁl may
improve perioperative feeding, early postoperative mobili-
sation, pain control, and respiratory physiotherapy; andhence reduce the risk of complications [ 16–18]. Ideally, the
patient should meet with the surgeon, anaesthetist and nurse.
Summary and
recommendationPatients should receive dedicated
preoperative counselling routinely.
Evidence level LowRecommendation grade Strong
M. Scha ¨fer /C1N. Demartines
Department of Visceral Surgery, University Hospital ofLausanne (CHUV), Lausanne, Switzerland
D. N. Lobo
Division of Gastrointestinal Surgery, Nottingham DigestiveDiseases Centre National Institute for Health Research
Biomedical Research Unit, Nottingham University Hospitals,
Queen’s Medical Centre, Nottingham, United Kingdom
M. Braga
San Raffaele University, Milan, ItalyO. Ljungqvist
Department of Surgery, O ¨rebro University Hospital, O ¨rebro,
Sweden
O. Ljungqvist
Department of Molecular Medicine and Surgery, Karolinska
Institutet, Stockholm, SwedenWorld J Surg (2013) 37:240–258 241
123

Table 1 Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS/C210) Society recommendations
Item Summary and recommendations Evidence level Recommendation
grade
Preoperative counselling Patients should receive dedicated preoperative counselling
routinelyLow Strong
Perioperative biliary drainage Preoperative endoscopic biliary drainage should not be
undertaken routinely in patients with a serum bilirubin
concentration \250lmol/lModerate Weak
Preoperative smoking and
alcohol consumptionFor alcohol abusers, 1 month of abstinence before surgery is
beneﬁcial and should be attempted. For daily smokers,
1 month of abstinence before surgery is beneﬁcial. For
appropriate groups, both should be attemptedAlcohol abstention:
lowStrong
Smoking cessation:
moderate
Preoperative nutrition Routine use of preoperative artiﬁcial nutrition is not warranted,
but signiﬁcantly malnourished patients should be optimizedwith oral supplements or enteral nutrition preoperativelyVery low Weak
Perioperative oral
immunonutrition (IN)The balance of evidence suggests that IN for 5–7 days
perioperatively should be considered because it may reduce the
rate of infectious complications in patients undergoing majoropen abdominal surgeryModerate Weak
Oral bowel preparation Extrapolation of data from studies on colonic surgery and
retrospective studies in PD show that MBP has no proven
beneﬁt. MBP should not be usedModerate Strong
Preoperative fasting and
preoperative treatment withcarbohydratesIntake of clear ﬂuids up to 2 h before anaesthesia does not
increase gastric residual volume and is recommended beforeelective surgery. Intake of solids should be withheld 6 h before
anaesthesia. Data extrapolation from studies in major surgery
suggests that preoperative oral carbohydrate treatment shouldbe given in patients without diabetesFluid intake: high Fasting: strong
carbohydrateloading: strongSolid intake: low
Carbohydrate
loading: low
Preanaesthetic medication Data from studies on abdominal surgery show no evidence of
clinical beneﬁt from pre-operative use of long-acting
sedatives, and they should not be used routinely. Short-acting
anxiolytics may be used for procedures such as insertion ofepidural cathetersNo long-acting
sedatives: moderateWeak
Anti-thrombotic prophylaxis LMWH reduces the risk of thromboembolic complications, and
administration should be continued for 4 weeks after hospital
discharge. Concomitant use of epidural analgesia necessitatesclose adherence to safety guidelines. Mechanical measuresshould probably be added for patients at high riskHigh Strong
Antimicrobial prophylaxis
and skin preparationAntimicrobial prophylaxis prevents surgical-site infections, and
should be used in a single-dose manner initiated 30–60 min
before skin incision. Repeated intraoperative doses may benecessary depending on the half-life of the drug and duration
of procedureHigh Strong
Epidural analgesia Mid-thoracic epidurals are recommended based on data from
studies on major open abdominal surgery showing superiorpain relief and fewer respiratory complications compared withintravenous opioidsPain: high Weak
Reduced respiratory
complications:moderate
Overall morbidity:
low
Intravenous analgesia Some evidence supports the use of PCA or intravenous lidocaine
analgesic methods. There is insufﬁcient information onoutcome after PDPCA: very low Weak
I.V. Lidocaine:
moderate
Wound catheters and
transversus abdominis plane
blockSome evidence supports the use of wound catheters or TAP
blocks in abdominal surgery. Results are conﬂicting and
variable, and mostly from studies on lower gastrointestinal
surgeryWound catheters:
moderateWeak
TAP blocks:
moderate242 World J Surg (2013) 37:240–258
123

Table 1 continued
Item Summary and recommendations Evidence level Recommendation
grade
Postoperative nausea and
vomiting (PONV)Data from the literature on gastrointestinal surgery in patients at
risk of PONV show the beneﬁts of using different
pharmacological agents depending on the patient’s PONV
history, type of surgery and type of anaesthesia. Multimodalintervention during and after surgery is indicatedLow Strong
Incision The choice of incision is at the surgeon’s discretion, and should
be of a length sufﬁcient to ensure good exposureVery low Strong
Avoiding hypothermia Intraoperative hypothermia should be avoided by using
cutaneous warming, i.e., forced-air or circulating-water
garment systemsHigh Strong
Postoperative glycaemic
controlInsulin resistance and hyperglycaemia are strongly associated
with postoperative morbidity and mortality. Treatment of
hyperglycaemia with intravenous insulin in the ICU setting
improves outcomes but hypoglycaemia remains a risk. SeveralERAS protocol items attenuate insulin resistance and facilitateglycaemic control without the risk of hypoglycaemia.
Hyperglycaemia should be avoided as far as possible without
introducing the risk of hypoglycaemiaLow Strong
Nasogastric intubation Pre-emptive use of nasogastric tubes postoperatively does not
improve outcomes, and their use is not warranted routinelyModerate Strong
Fluid balance Near-zero ﬂuid balance, avoiding overload of salt and water
results in improved outcomes. Perioperative monitoring of
stroke volume with transoesophageal Doppler to optimizecardiac output with ﬂuid boluses improves outcomes. Balancedcrystalloids should be preferred to 0.9 % salineFluid balance: high
oesophageal
doppler: moderateStrong
Balanced crystalloids
vs. 0.9 % saline:moderate
Perianastomotic drain Early removal of drains after 72 h may be advisable in patients
at low risk (i.e., amylase content in drain \5,000 U/L) for
developing a pancreatic ﬁstula. There is insufﬁcient evidenceto recommend routine use of drains, but their use is based only
on low-level evidenceEarly removal: high Early removal:
strong
Somatostatin analogues Somatostatin and its analogues have no beneﬁcial effects on
outcome after PD. In general, their use is not warranted.Subgroup analyses for variability in the texture and duct size
of the pancreas are not availableModerate Strong
Urinary drainage Suprapubic catheterisation is superior to transurethral
catheterisation if used for [4 days. Transurethral catheters can
be removed safely on postoperative day 1 or 2 unless otherwiseindicatedHigh For suprapubic:
weak
Transurethral
catheter out POD1–2: strong
Delayed gastric emptying
(DGE)There are no acknowledged strategies to avoid DGE. Artiﬁcial
nutrition should be considered selectively in patients withDGE of long durationVery low Strong
Stimulation of bowel
movementA multimodal approach with epidural and near-zero ﬂuid
balance is recommended. Oral laxatives and chewing gum
given postoperatively are safe, and may accelerate
gastrointestinal transitLaxatives: very low Weak
Chewing gum: low
Postoperative artiﬁcial
nutritionPatients should be allowed a normal diet after surgery without
restrictions. They should be cautioned to begin carefully and
increase intake according to tolerance over 3–4 days. Enteral
tube feeding should be given only on speciﬁc indications andparenteral nutrition should not be employed routinelyEarly diet at will:
moderateStrong
Early and scheduled
mobilisationPatients should be mobilized actively from the morning of the
ﬁrst postoperative day and encouraged to meet daily targets for
mobilisationVery low Strong
Audit Systematic improves compliance and clinical outcomes Low StrongWorld J Surg (2013) 37:240–258 243
123

Preoperative biliary drainage
Five meta-analyses [ 19–23], and two articles from a ran-
domised controlled trial (RCT) not included in the meta-
analyses [ 24,25], assessed the role of biliary drainage
before PD. The ﬁrst meta-analysis from 2002 [ 19], inclu-
ded randomised ( n=5) and non-randomised trials
(n=18). A Cochrane review [ 21] included 5 randomised
trials, but considered all 5 trials to have a risk of bias,
thereby weakening the conclusions reached. Of the trials
included, 4 evaluated percutaneous drainage and 1 evalu-ated endoscopic drainage. The Cochrane review concluded
that preoperative biliary drainage did not decrease mor-
tality in patients with obstructive jaundice. Although therewas a trend towards decreased postoperative morbidity, the
increased risk of procedure-related complications coun-
terbalanced this possible beneﬁt (especially for percuta-neous drainage). The ﬁndings of the Cochrane review were
in accordance with those of the other meta-analyses, sug-
gesting that preoperative drainage confers neither beneﬁt
nor harm. One recent RCT not included in the meta-
analyses [ 24] (and which included patients with serum
bilirubin concentrations \250lmol/l) showed increased
morbidity in patients undergoing preoperative biliary
drainage (endoscopic primarily; percutaneous as rescueoption), but the delay in surgery did not affect overall
survival [ 25].
Summary and
recommendationPreoperative endoscopic biliary
drainage should not be carried
out routinely in patients with a
serum bilirubin concentration\250lmol/l
Evidence level Moderate
Recommendation grade Weak
Preoperative smoking and alcohol consumption
Overall postoperative morbidity is increased by two- to
threefold in alcohol abusers [ 26]. Also, 1 month of pre-
operative abstinence has been shown to signiﬁcantlyimprove outcome in a group who took ‘‘ﬁve or more drinks
(60 g of ethanol) a day without clinical or historical evi-
dence of alcohol related illness’’ [ 27].
Daily smokers ( [2 cigarettes daily for C1 year) have an
increased risk of pulmonary and wound complications [ 28,
29]. RCTs have demonstrated reductions in the rates of
both types of complications 1 month after cessation of
smoking [ 29,30].
Summary and
recommendationFor alcohol abusers, 1 month of absti-
nence before surgery is beneﬁcial andshould be attempted. For daily smokers,
1 month of abstinence before surgery is
beneﬁcial. For appropriate groups, bothshould be attempted
Evidence level Alcohol abstention: Low; Smoking
cessation: Moderate
Recommendation
gradeStrong
Preoperative nutrition
In western countries, patients scheduled for PD are, in
general, not malnourished, and usually present with \
7%
weight loss [ 31]. In such cases, preoperative artiﬁcial
nutrition is not warranted. The situation may be different in
other regions. It is widely accepted that signiﬁcantly mal-
nourished patients suffer increased postoperative morbidityafter major surgery [ 32–34]. Preoperative supplements
with oral sip feeds or enteral tube feeds are usually
administered in these cases, but scientiﬁc evidence tosupport this routine (as opposed to no nutritional support)
is lacking. Extrapolating data from studies in the postop-
erative setting suggests that parenteral nutrition should beused only if the enteral route is inaccessible.
Summary and
recommendationRoutine use of preoperative artiﬁcial
nutrition is not warranted, but signif-icantly malnourished patients should
be optimized with oral supplements or
enteral nutrition preoperatively
Evidence level Very low
Recommendation
gradeWeak
Perioperative oral immunonutrition (IN)
The role of IN has been investigated thoroughly over many
years. Few studies speciﬁcally address IN for PD patients,
and the variation in active immune-modulating nutrients
administered makes interpretation difﬁcult. A reduction inthe prevalence of infectious complications is a consistent
ﬁnding in patients with gastrointestinal cancer, as are
beneﬁcial effects on surrogate endpoints [levels of inter-leukins and C-reactive protein (CRP)] or LOSH. A
reduction in mortality has not been shown. Several recently
published reviews and meta-analyses [ 35–41] conclude that
there is a beneﬁt from perioperative and postoperative IN
in patients undergoing major gastrointestinal surgery, but
results remain inconsistent [ 42–44]. Beneﬁcial outcomes
have been shown in a systematic review of 35 trials in
patients undergoing elective surgery, in which arginine-
supplemented diets were associated with a signiﬁcantly244 World J Surg (2013) 37:240–258
123

reduced prevalence of infectious complications and LOSH
[45]. There is also evidence to suggest that immune-mod-
ulating nutrition may be more beneﬁcial in undernourished
rather than in normally nourished patients. However, INcould be detrimental in patients with sepsis [ 46]. There are
no trials investigating IN within ERAS care pathways.
Summary and
recommendationThe balance of evidence suggests that
IN for 5–7 days perioperatively should
be considered because it may reducethe prevalence of infectious compli-
cations in patients undergoing major
open abdominal surgery
Evidence level Moderate
Recommendation
gradeWeak
Oral bowel preparation
Mechanical bowel preparation (MBP) may lead to dehy-
dration and offset ﬂuid and electrolyte balance, particularlyin the elderly [ 47]. Meta-analyses from colonic surgery
have not shown clinical beneﬁt from MBP [ 48,49]. A large
and recent retrospective analysis of 200 consecutivepatients undergoing PD did not ﬁnd any beneﬁt of MBP to
a clear liquid diet the day before surgery [ 50]. No trial has
compared MBP to a regimen without MBP and an unre-stricted diet until midnight before surgery.
Summary and
recommendationExtrapolation of data from
colonic surgery and retrospectivestudies in PD show that MBP has
no proven beneﬁt. MBP should
not be used
Evidence level Moderate
Recommendation grade Strong
Preoperative fasting and preoperative treatment
with carbohydrates
Fasting from midnight has been standard practice in elective
surgery, but is not supported by evidence [ 51]. Overnight
fasting increases insulin resistance and discomfort after
abdominal surgery [ 52,53]. Guidelines recommend the
intake of clear ﬂuids up to 2 h before the induction ofanaesthesia as well as a fasting period of 6 h for solids [ 54].
The latter recommendation has a weak scientiﬁc basis [ 55].
Intake of a complex clear carbohydrate-rich drink designedfor preoperative use B2 h before the induction of anaesthesia
has been shown to reduce hunger, thirst and anxiety, and to
decrease postoperative insulin resistance [ 56–58]. Earlierresumption of gut function after colorectal surgery has also
been suggested [ 59], and an RCT including some PD patients
concluded that oral carbohydrate treatment may preserve
skeletal muscle mass [ 60]. An RCT conducted in patients
undergoing cholecystectomy did not show any beneﬁt [ 61].
Data on the safety and clinical beneﬁt of preoperative car-
bohydrate in patients with diabetes are sparse [ 62,63], and
further research is warranted in this group.
Summary and
recommendationIntake of clear ﬂuids up to 2 h before
anaesthesia does not increase gastric
residual volume and is recommended
before elective surgery. Intake ofsolids should be withheld 6 h before
anaesthesia. Data extrapolation from
studies in major surgery suggests thatpreoperative oral carbohydrate
treatment should be given in patients
without diabetes
Evidence level Fluid intake: High Solid intake: Low;
Carbohydrate loading: Low
Recommendation
gradeFasting: Strong Carbohydrate loading:
Strong
Pre-anaesthetic medication
Anxiety makes postoperative pain more difﬁcult to control.
Pre-emptive treatment of anxiety could lower pain scores
and reduce the demand for opiates [ 64]. However, pre-
induction anxiolytic medication increases postoperative
sedation [ 65], and a meta-analysis did not demonstrate
reduced postoperative pain with pre-emptive use of anal-gesics [ 66]. Short-acting anxiolytics may be helpful in
some patients during placement of an epidural catheter, and
experiences from day surgery suggest that cognitive func-tion is not signiﬁcantly impaired [ 67]. Additionally, oral
ﬂuids and a carbohydrate-rich beverage have been shown
to reduce preoperative anxiety [ 57]. Medications for
chronic pain need to be continued on the morning of sur-
gery, and should be prescribed in the postoperative period.
Summary and
recommendationData from studies on abdominal surgery
show no evidence of clinical beneﬁt
from preoperative use of long-actingsedatives, and they should not be used
routinely. Short- acting anxiolytics may
be used for procedures such as insertionof epidural catheters
Evidence level No long-acting sedatives: Moderate
RecommendationgradeWeakWorld J Surg (2013) 37:240–258 245
123

Anti-thrombotic prophylaxis
Malignant disease and major surgery increase the risk of
venous thromboembolism (VTE) [ 68]. Unfractionated and
fractionated low-dose heparins are effective at preventingVTE [ 69]. Fractionated low-molecular-weight heparin
(LMWH) is preferable in view of compliance (once-daily
administration) [ 70]. Treatment is usually initiated 2–12 h
before surgery and continued until patients are fully
mobile. A meta-analysis supports continued treatment for
4 weeks after hospital discharge [ 71]. Concomitant use of
LMWH and epidural catheters is controversial [ 72–75]. It
has, therefore, been recommended that the catheter be
inserted C12 h after a dose of LMWH, and removed C12 h
after administration of LMWH [ 76]. The risk of an epidural
or spinal haematoma is increased in patients who are also
on anti-platelet drugs or oral anticoagulants [ 73]. Com-
bined prophylactic modalities have been shown to be
superior to pharmacological measures only in preventing
VTE [ 77]. Mechanical intermittent pneumatic leg com-
pression [ 77], and elastic stockings may be used as adjuncts
in patients who are at moderate or high risk for VTE [ 78].
Summary and
recommendationLMWH reduces the risk of throm-
boembolic complications. Adminis-
tration should be continued for
4 weeks after hospital discharge.
Concomitant use of epidural analgesia
necessitates close adherence to safetyguidelines. Mechanical measures
should probably be added for patients
at high risk
Evidence level High
Recommendation
gradeStrong
Antimicrobial prophylaxis and skin preparation
There is ample evidence favouring the prescription of
antimicrobial prophylaxis for major abdominal procedures
[79,80]. Trials speciﬁcally targeting patients undergoing
PD were not identiﬁed. Recently published studies reported
or recommended prescription in a single-dose manner [ 80].
However, an extra dose should be provided every 3–4 hduring the procedure if drugs with a short half-life are
chosen [ 81]. Initial administration should be as near as
possible to the skin incision and B1 h before the incision
[79,82]. The choice of antibiotic is dependent upon local
guidelines, and should be different from the drug of choice
for treatment of established infections. Skin preparation
with a scrub of chlorhexidine-alcohol has recently been
claimed to be superior to povidone-iodine in preventingsurgical-site infections [ 83]. However, the difference islikely to be very small because excellent results are
obtained with povidone-iodine [ 84]. Alcohol-based scrubs
have been reported to be used in ﬁre-based and burn
injuries [ 85].
Summary and
recommendationAntimicrobial prophylaxis prevents
surgical-site infections and should be
used in a single-dose manner initiated
30–60 min before skin incision.
Repeated intraoperative doses may benecessary depending on the half-life of
the drug and duration of the procedure
Evidence level HighRecommendation
gradeStrong
Epidural analgesia
A meta-analysis showed that continuous epidural analgesia
with or without opioids provided signiﬁcant improvement
in postoperative pain control compared with parenteralopioids in open abdominal surgery [ 86]. Moreover, a
Cochrane review demonstrated that continuous epidural
analgesia is superior to patient-controlled intravenousopioid analgesia in relieving pain B72 h after open
abdominal surgery [ 87]. A decreased prevalence of ileus
was found for epidural administration of local anaestheticafter laparotomy compared with systemic or epidural
opioids in one Cochrane review [ 88]. With respect to
complications after abdominal or thoracic surgery, a meta-analysis [ 89] concluded that epidural analgesia was asso-
ciated with a signiﬁcantly decreased risk of postoperative
pneumonia, as well as an improvement in pulmonaryfunction and arterial oxygenation. Also, the use of epidu-
rals has been shown to reduce insulin resistance [ 90].
Despite the widespread use of epidural analgesia afterpancreatic surgery [ 91], RCTs that speciﬁcally examine the
outcomes of epidural analgesia after pancreatic surgery are
lacking. A retrospective study comparing epidural analge-sia with intravenous analgesia after PD found that patients
with epidural analgesia had lower pain scores but signiﬁ-
cantly higher rates of major complications [ 92]. It has been
suggested that thoracic epidural analgesia after PD is
associated with haemodynamic instability, which might
compromise enteric anastomoses, intestinal perfusion andrecovery of gastrointestinal function [ 92]. In experimental
acute pancreatitis and in sepsis, however, thoracic epidu-
rals improved perfusion in gastrointestinal mucosal capil-laries [ 93]. The adverse perfusion effects of epidural
analgesia appear to be related to the prolonged and
extended sympathetic block. This would imply that thebeneﬁcial effects of epidural analgesia can be preserved as
long as the haemodynamic consequences are adequately246 World J Surg (2013) 37:240–258
123

controlled with vasopressors [ 94]. Concerns about anasto-
moses have been raised after colorectal surgery, but one
meta-analysis did not detect differences in rates of anas-
tomotic leaks between patients receiving postoperativelocal anaesthetic epidurals and those receiving systemic or
epidural opioids [ 95].
A potential drawback with epidurals is that as many as
one-third of epidurals may not function satisfactorily in
some centres [ 96,97]. Possible reasons may be that:
catheters are not located in the epidural space; the insertion
level does not cover the surgical incision; the dosage of
local anaesthetic and opioid are insufﬁcient; or pumpfailure. For upper transverse incisions, epidural catheters
should be inserted between T5 and T8 root levels. Sensory
block should be tested (cold and pinprick) before inductionof general anaesthesia. Efforts should be made to check the
sensory block on a daily (or more frequent) basis, and the
infusion should be adjusted to provide sufﬁcient analgesiato allow mobilisation out of bed. It has been suggested that
epidural analgesia should continue for C48 h and, after a
successful stop-test, oral multimodal analgesia with para-cetamol and non-steroidal anti-inﬂammatory drugs (NSA-
IDS)/cyclooxygenase (COX)-2 inhibitors should be
commenced together with oral opioids as required. Func-tioning epidural catheters may be used for a longer duration
if needed. Further studies are warranted to evaluate spe-
ciﬁcally the potential risks and beneﬁts of epidural anal-gesia after pancreatic surgery. The use of epidurals has not
been investigated for laparoscopic pancreatic resections.
Summary and
recommendationMid-thoracic epidurals are recom-
mended based on data from studies
on major open abdominal surgery
showing superior pain relief and
fewer respiratory complications com-
pared with intravenous opioids
Evidence level Pain: High; Reduced respiratory
complications: Moderate; Overall
Morbidity: Low
Recommendation
gradeWeak
Intravenous analgesia
Thoracic epidural anaesthesia remains the ‘gold standard’
method for major open abdominal surgery, but there are
situations in which it cannot be employed. Patient-con-
trolled analgesia (PCA) with opioids is the most commonmodality used as an alternative to an epidural. In a clinical
trial on the implementation of a critical pathway for distal
pancreatic surgery, PCA was the only analgesic modalityused, but no comments were made on the impact of sys-
temic analgesia on accelerating recovery [ 98].Intravenous infusion of lidocaine has analgesic, anti-
inﬂammatory and antihyperalgesic properties, and has been
evaluated as an analgesic modality for abdominal surgery.
A systematic review of 8 trials (161 patients) in which thecontinuous infusion of lidocaine was compared with PCA
morphine for abdominal surgery, showed a decrease in the
duration of ileus, LOSH, postoperative pain intensity andside effects [ 99]. A recent RCT in patients undergoing
laparoscopic colorectal resection using the ERAS pro-
gramme showed no difference in return of gastrointestinal
function and LOSH between continuous infusion of lido-
caine and thoracic epidural anaesthesia [ 100].
Summary and
recommendationSome evidence supports the use of PCA
or intravenous lidocaine analgesic
methods. There is insufﬁcient informa-tion on outcome after PD
Evidence level PCA: Very Low; I.V. Lidocaine:
Moderate
Recommendation
gradeWeak
Wound catheters and transversus abdominis plane
(TAP) block
The efﬁcacy of wound infusion with local anaesthetic
agents as a postoperative analgesic method has been pro-ven in a meta-analysis of different surgical procedures
[101]. Conversely, a more recent meta-analysis showed
that wound catheters provided no signiﬁcant reduction inpain intensity (at rest or with activity) or in morphine
consumption at any time after laparotomy [ 102]. No sig-
niﬁcant differences in the prevalence of infectious com-plications were found. These inconsistent results might be
due to factors such as the type, concentration and dose of
local anaesthetic, type of catheter, mode of delivery, orcatheter location (subcutaneous or subfascial) [ 103]. In
patients undergoing colorectal surgery, a signiﬁcant opioid-
sparing effect and reduction of LOSH were demonstratedwhen local anaesthetic was infused through a catheter
positioned between the fascia and the peritoneum [ 104]. No
signiﬁcant increase in wound infections was found with the
insertion of a catheter and infusion of local anaesthetics.
No comparison has been made with other modalities (e.g.,
epidural analgesia) or in enhanced recovery programmes.
TAP blocks anaesthetise the thoracolumbar nerves
(intercostal, subcostal and ﬁrst lumbar), which provide
sensory innervation to the anterolateral abdominal wall.The ultrasonography-guided technique for TAP blocks has
been used for postoperative analgesia after abdominal
surgery. A systematic analysis of 7 studies (360 patients)showed signiﬁcant opioid-sparing in the postoperative
period [ 105]. A meta-analysis of 5 RCTs (176 patients)World J Surg (2013) 37:240–258 247
123

conﬁrmed previous results showing improved pain relief
and reduced opioid-associated side effects [ 106]. However,
no studies have compared TAP block with other analgesic
methods such as epidural analgesia or inﬁltration of localanaesthetic into the abdominal wound. Furthermore, no
studies have used an enhanced recovery programme [ 107]
and no studies have been conducted in patients undergoingpancreatic surgery.
The marked heterogeneity observed between studies
included in the meta-analyses mentioned above would
imply that further trials are needed to evaluate the potential
use of wound catheters and TAP blocks in pancreaticsurgery.
Summary and
recommendationSome evidence supports the use of wound
catheters or TAP blocks in abdom-inal surgery. Results are conﬂicting
and variable and mostly from studies
in lower gastrointestinal surgery
Evidence level Wound catheters: Moderate; TAP
blocks: Moderate
RecommendationgradeWeak
Postoperative nausea and vomiting (PONV)
Data speciﬁcally addressing PONV after PD speciﬁcally
have not been identiﬁed. One comparative (non-random-
ised) study [ 7] showed that an ERAS protocol with early
mobilisation, metoclopramide and removal of nasogastrictube on day 1 or day 2 decreased the rate of postoperative
nausea and vomiting. Until further documentation becomes
available, the suggestions for patients undergoing colo-rectal surgery [ 3] should be applicable to those undergoing
PD: Patients with two risk factors (female sex, non-
smoking status, history of motion sickness (or PONV) andpostoperative administration of opioids [ 108,109]) should
receive prophylaxis with dexamethasone at induction or a
serotonin receptor antagonist (e.g., ondansetron, tropise-tron) at the end of surgery [ 110]. High-risk individuals
(three factors) should receive general anaesthesia with
propofol and remifentanil and no volatile anaesthetics; anddexamethasone 4–8 mg at the beginning of surgery, sup-
plemented with serotonin receptor antagonists or droperi-
dol [ 110], or 25–50 mg metoclopramide 30–60 min before
the end of surgery [ 111]. Ondansetron can be used for
prophylaxis and treatment. A possible risk of impaired
anastomotic healing caused by single-dose dexamethasoneor other steroids perioperatively has been addressed clini-
cally and experimentally, but remains unclear [ 112–115].
Summary and
recommendationData from the literature on gastroin-
testinal surgery in patients at risk ofPONV show the beneﬁts of using dif-
ferent pharmacological agents depend-
ing on the patient’s PONV history, typeof surgery and type of anaesthesia.
Multimodal intervention, during and
after surgery is indicated
Evidence level Low
Recommendation
gradeStrong
Incision
There are no data comparing the types of incisions for
patients undergoing PD. The authors of these recommen-
dations are comfortable with straight transverse, curved
transverse and chevron incisions, indicating that all arepractical. Laparoscopic resection of the pancreatic head has
been reported to be feasible [ 116], but its future role is
uncertain.
Summary and
recommendationThe choice of incision is at the
surgeon’s discre-
tion, and should be of a lengthsufﬁcient to ensure good exposure
Evidence level Very Low
RecommendationgradeStrong
Avoiding hypothermia
Several meta-analyses and RCTs have demonstrated that
preventing inadvertent hypothermia during major
abdominal surgery (such as PD) reduces the prevalence of
wound infections [ 117,118], cardiac complications [ 118
–
120], bleeding and transfusion requirements [ 118–121], as
well as the duration of post-anaesthetic recovery [ 122].
Furthermore, extending systemic warming in the periop-erative period (2 h before and after surgery) has addi-
tional beneﬁts [ 123]. Hence, the use of active cutaneous
warming is highly recommended to reduce postoperativemorbidity and enhance recovery. There is even evidence
to suggest that circulating-water garments offer better
temperature control than forced-air warming systems[124–126].
Summary and
recommendationIntraoperative hypothermia should be
avoided by using cutaneous warming,
i.e., forced-air or circulating-water
garment systems
Evidence level High
Recommendation
gradeStrong248 World J Surg (2013) 37:240–258
123

Postoperative glycaemic control
Postoperative hyperglycaemia in patients without diabetes
is a result of acquired insulin resistance. Morbidity and
mortality after major abdominal surgery have been asso-ciated with increasing levels of insulin resistance [ 127] and
plasma glucose [ 128]. Such an association has also been
demonstrated in pancreatic surgery [ 129]. Data from
patients subjected to colorectal surgery within an ERAS
regimen indicate that higher preoperative levels of glycated
haemoglobin (HBA1c) and higher postoperative levels ofglucose also predict postoperative morbidity [ 130].
Core elements of ERAS protocols attenuate postopera-
tive insulin resistance and thus also lower glucose levels[131,132]. The most obvious (of several) protocols are
avoidance of preoperative fasting and oral bowel prepara-
tion; use of oral carbohydrate treatment and stimulation ofearly resumption of gut function by optimal ﬂuid balance
and avoidance of systemic opioids; and the reduction of the
stress response by use of epidural anaesthesia.
Reducing the rate of hyperglycaemia in surgical patients
in intensive-care settings has been documented to reducethe rate of complications [ 133–136]. Similar trials in ward
settings in patients treated with modern care regimens are
wanting. The target concentration for plasma glucose iscontroversial [ 137], but it seems fair to advocate that hy-
perglycaemia should be avoided and that this will improve
outcome irrespective of the baseline level. Achieving tightglycaemic control with intravenous insulin is challenging
in the ward setting because of the risk of hypoglycaemia.
Glucosuria with the risk of hypovolaemia will ensue whenthe renal threshold is passed at [12 mmol/l [ 137]. This
level has been used as the control regimen in seminal trials
[133,138] and should probably be regarded as a limit
irrespective of settings to avoid additional disturbances in
ﬂuid balance.
Summary and
recommendationInsulin resistance and hyperglycaemia
are strongly associated with postoper-
ative morbidity and mortality. Treat-
ment of hyperglycaemia with intrave-nous insulin in the intensive-care setting
improves outcomes but hypoglycaemia
remains a risk. Several ERAS protocolitems attenuate insulin resistance and
facilitate glycaemic control without the
risk of hypoglycaemia. Hyperglyca-
emia should be avoided as far as
possible without introducing the riskof hypoglycaemia
Evidence level Low
RecommendationgradeStrongNasogastric intubation
There is strong evidence that routine nasogastric decom-
pression after elective laparotomy should be avoided [ 139].
Fever, atelectasis and pneumonia occur more frequently inpatients with a nasogastric tube than in those without [ 139,
140]. Bowel function returns earlier in patients if naso-
gastric decompression is avoided [ 139]. Gastro-oesopha-
geal reﬂux is increased during laparotomy if nasogastric
tubes are inserted [ 141]. The role of nasogastric tubes has
not been investigated prospectively in pancreatic surgery.However, the abundant high-level evidence in other ﬁelds
of abdominal surgery, including gastroduodenal surgery
[139], should allow for an extrapolation to patients
undergoing PD and justify a ‘no decompressive nasogastric
tube’ policy. This is also supported by some series with
historic controls [ 142,143]. A large Norwegian RCT in
patients after upper gastrointestinal and hepatopancreati-
cobiliary surgery (and including [80 patients who had
undergone PD and were treated without routine use of a
nasogastric tube) found that early oral feeding was safe and
feasible [ 144]. This has also been corroborated by other
non-randomised, fast-track implementation series in this
ﬁeld [ 5–7,9]. In keeping with data in other areas of gas-
trointestinal surgery, nasogastric decompression tubes hadto be replaced in B15 % of patients [ 6,7,9]. Nasogastric
tubes placed during surgery (to evacuate air) should be
removed before the reversal of anaesthesia. Delayed gastricemptying is a speciﬁc problem in &10–25 % of patients
after PD [ 6,7,9] and it may be necessary to
insert a decompression tube in a minority of patientspostoperatively.
Summary and
recommendationPre-emptive use of nasogastric
tubes postoperatively does notimprove outcomes and their use
is not warranted routinely
Evidence level Moderate
Recommendation grade Strong
Fluid balance
Patients undergoing abdominal surgery often receive
excessive volumes of intravenous ﬂuids during and in the
days after surgery. This frequently exceeds actual ﬂuid
losses, resulting in a weight gain of 3–6 kg [ 145,146].
Excessive overload of salt and water in the perioperative
period increases postoperative complication rates and
delays the return of gastrointestinal function [ 146–149].
This strongly suggests that near-zero ﬂuid balance must be
achieved perioperatively. Identifying the correct amount
needed is a challenge that is also complicated by the use ofWorld J Surg (2013) 37:240–258 249
123

epidural analgesia, which causes vasodilatation and intra-
vascular hypovolaemia with hypotension, which is often
interpreted and treated as ﬂuid depletion. The result is
copious volumes of ﬂuid administration when a vasopres-sor would be preferable [ 150]. In a meta-analysis of elec-
tive colorectal patients, intraoperative ﬂow-guided ﬂuid
therapy with trans-oesophageal Doppler (TOD) ultraso-nography to accurately assess and monitor ﬂuid status in
relation to cardiac output reduced complications and LOSH
[151]. Other methods, such as lithium dilution (LiDCO) are
evolving and may prove to be equivalent to TOD.
Hyperchloraemic acidosis results from infusion of 0.9 %
saline. Recent studies have shown that excessive use of
0.9 % saline leads to renal oedema, reduced ﬂow velocity
in the renal artery, renal cortical tissue perfusion [ 152], and
an overall increase in postoperative complications when
compared with balanced crystalloids [ 153]. A recent meta-
analysis [ 154] has suggested that postoperative complica-
tions and LOSH are signiﬁcantly reduced if patients
undergoing major abdominal surgery are maintained in
ﬂuid balance rather than ﬂuid imbalance. The meta-anal-ysis concluded that too much and too little ﬂuid is detri-
mental to outcome. Although colloids produce better blood
volume expansion and less interstitial space overload thancrystalloids [ 155], there is no evidence from clinical trials
and meta-analyses that colloids result in better clinical
outcome than crystalloids [ 156]. To avoid unnecessary
ﬂuid overload, vasopressors should be considered for intra-
and postoperative management of epidural-induced
hypotension.
Summary and
recommendationNear-zero ﬂuid balance as well as
avoiding overload of salt and water
results in improved outcomes. Peri-
operative monitoring of stroke volume
with trans-oesophageal Doppler tooptimize cardiac output with ﬂuid
b o l u s e si m p r o v e so u t c o m e s .B a l a n c e d
crystalloids should be preferred to0.9 % saline
Evidence level Fluid balance: High; Oesophageal
Doppler: Moderate; Balanced crystal-loids vs. 0.9 % saline: Moderate
Recommendation
gradeStrong
Perianastomotic drains
Perianastomotic drains are believed to ameliorate the
consequences of minor leaks and allow them to be treated
as controlled ﬁstulas. One RCT comparing suction drain tono drain after pancreatic cancer resection did not show
signiﬁcant differences in terms of mortality or overallcomplication rate [ 157]. Moreover, patients who used these
drains had a signiﬁcantly greater incidence of intra-
abdominal collections or ﬁstulas (pancreatic and entero-
cutaneous) [ 157]. A series with historic controls failed to
identify any increased risk after a no-drain regimen, but
this design is prone to selection bias [ 158]. Evaluation of
early (postoperative day 3) versus late (postoperative day 5and beyond) drain removal has been examined in an RCT
[159]. Early removal of the drain in patients at low risk of
pancreatic ﬁstula (amylase value in drains \5,000 U/L at
postoperative day 3) was associated with a signiﬁcantly
decreased rate of pancreatic ﬁstula, abdominal and pul-monary complications. Until further data are available, a
conservative approach with systematic postoperative
drainage and early removal in patients at low risk of pan-creatic ﬁstula (ﬁrm pancreas, wide pancreatic duct [ 159–
161]) is recommended. In accordance with this notion, it
would seem wise to place a drain in patients with a softpancreas and narrow duct, and leave this drain in situ
slightly longer.
Summary and
recommendationEarly drain removal after 72 h may be
advisable in patients at low risk (i.e.,
amylase content in drain \5,000 U/L)
for developing a pancreatic ﬁstula. Thereis insufﬁcient evidence to recommend no
routine use of drains routinely, but their
use is based only on low-level evidence
Evidence level Early removal: High
Recommendation
grade
Early removal: Strong
Somatostatin analogues
Somatostatin and its synthetic analogues (e.g., octreotide)
reduce splanchnic blood ﬂow and the release of pancreaticexocrine secretion [ 162]. The rationale for its use is to
reduce the risk of pancreatic anastomotic ﬁstulas by
decreasing the volume of pancreatic exocrine secretions.Several RCTs have resulted in four systemic reviews and
meta-analyses that assessed the possible role of a protec-
tive effect in pancreatic surgery [ 163–166]. The most
recent meta-analysis involved 17 trials with 1,457 patients
undergoing PD and 686 undergoing distal or other resec-
tions [ 166]. The authors concluded that the use of
somatostatin analogues reduced the crude rate of pancre-
atic ﬁstulas, but that the rate of clinically signiﬁcant ﬁs-
tulas as well as the overall major morbidity and mortalityremained unchanged [ 166]. Subgroup analyses of the PD
patients showed no signiﬁcant effect of somatostatin/
octreotide on any of the reported outcomes [ 166]. The
beneﬁcial effect of somatostatin commonly believed to be
present in cases with acknowledged risk factors (soft250 World J Surg (2013) 37:240–258
123

pancreas, small pancreatic duct) is not substantiated by the
available evidence.
Summary and
recommendationSomatostatin and its analogues have
no beneﬁcial effects on outcome after
PD. In general, their use is not
warranted. Subgroup analyses for thevariability in the texture and duct size
of the pancreas are not available
Evidence level ModerateRecommendation
gradeStrong
Urinary drainage
A meta-analysis of RCTs on urinary drainage after surgery
showed that suprapubic catheterisation was superior to
transurethral catheterisation [ 167]. Patients found supra-
pubic catheters more acceptable, and morbidity was
reduced [ 167]. Most trials in the meta-analysis evaluated
urinary drainage for 4–7 days. The only trial in the meta-analysis focusing speciﬁcally on hepatopancreaticobiliary
surgery [ 168] included 82 such patients out of a total of
146. The number of patients undergoing PD was not stated.The authors found no difference in outcomes, but argued
that suprapubic catheterisation is probably superior; how-
ever, the difference is likely to be small. A recent RCTwith a large number of patients undergoing major surgery
with thoracic epidurals found removal of transurethral
catheter on postoperative day 1 to be superior in terms ofinfection rates and did not lead to an increased rate of re-
catheterisation when compared with removal on day 3–5
[169].
Summary and
recommendationSuprapubic catheterisation is superior to
transurethral catheterisation if used for[4 days. Transurethral catheters can be
removed safely on postoperative day 1
or 2 unless otherwise indicated
Evidence level High
Recommendation
gradeFor suprapubic: Weak; Transurethral
catheter out postoperative day 1–2:Strong
Delayed gastric emptying (DGE)
DGE is a speciﬁc problem after PD occurring in &10–25 % of
patients [ 6,7,9,170]. It may be necessary to insert a nas-
ojejunal feeding tube in a minority of patients. DGE is as
common after pylorus-preserving PD as after a classic
Whipple’s procedure [ 171]. In this context, DGE was less
common in a fast-track group compared with a traditional caregroup in one study [ 7]. For pylorus-preserving PDs, it has been
shown that constructing the duodenojejunostomy in an ante-
colic (as opposed to a retro-colic) fashion results in less DGE
[172]. Occasionally, DGE persists and may necessitate enteral
feeding delivered beyond the gastrojejunostomy (or even
parenteral nutrition). The available deﬁnition of DGE [ 170]i s
based on the assessed need for nasogastric tubes. The entity issusceptible to being over-diagnosed, and care should be taken
to ensure that it does not encourage the insertion of nasogastric
tubes as routine practice.
Summary and
recommendationThere are no acknowledged strategies
to avoid DGE. Artiﬁcial nutritionshould be considered selectively in
patients with DGE of long duration
Evidence level Very lowRecommendation
gradeStrong
Stimulation of bowel movement
There is no high-level evidence to support a speciﬁc
motility-enhancing drug. A multimodal approach involvingthe use of oral laxatives such as magnesium sulphate or
bisacodyl may induce early gastrointestinal transit after
colonic resections [ 173,174]. Some protocols for fast-track
pancreatic surgery have recommended the use of laxatives
postoperatively [ 175
]. In a series of 255 pancreatic resec-
tions (almost 60 % PDs), oral administration of magnesium(200 mg/day) and lactulose in addition to metoclopramide
on postoperative day 1 to support early start of normal
bowel function was advocated [ 6]. Along with other mul-
timodal prescriptions, the authors concluded that this pro-
tocol was associated with a low prevalence of re-admission
to hospital, mortality, and morbidity rates [ 6]. However, no
randomised trial has investigated the use of oral laxatives,
so further studies are necessary. As noted above, the
appropriate use of epidurals and maintaining a near-zeroﬂuid balance are associated with an enhanced return of
bowel activity after abdominal surgery [ 88,146]. Chewing
gum has been shown to be safe and beneﬁcial in restoringgut activity after colorectal surgery [ 176–178]
Summary and
recommendationA multimodal approach with epidural and
near-zero ﬂuid balance is recommended.
Oral laxatives and chewing gum given
postoperatively are safe and may accel-erate gastrointestinal transit
Evidence level Laxatives: Very low; Chewing gum:
Low
Recommendation
gradeWeakWorld J Surg (2013) 37:240–258 251
123

Postoperative artiﬁcial nutrition
Most patients tolerate normal oral intake soon after elective
PD. Early oral intake in this patient group has been shown
to be feasible and safe [ 6,144]. A recent large multicentre
RCT in patients undergoing only major upper gastrointes-
tinal and hepatopancreaticobiliary surgery (including [80
patients undergoing PD) investigated this issue and con-cluded that allowing early diet is safe for these patients and
that enteral tube feeding did not confer beneﬁt [ 144]. This
is in keeping with other reports, [ 179] including enteral
tube feeding after other major abdominal surgery [ 180].
There are no data to support the idea that a surgeon-con-
trolled stepwise increase from spoonfuls of water to anormal diet is safer than a patient-controlled routine as long
as patients are informed about the potential of impaired gut
function in the early postoperative period. Enteral or par-enteral nutritional support will often be necessary if major
complications develop. Parenteral nutrition is indicated
only in those patients who cannot eat and drink normally,and who in addition cannot tolerate enteral nutrition [ 181].
Parenteral nutrition should be reduced as the tolerance of
enteral nutritional intake increases.
Enteral tube feeding delivers artiﬁcial nutrients, but is a
non-volitional intervention that bypasses the cephalic-
vagal digestive reﬂex and carries signiﬁcant risks [ 182,
183]. Traditionally, beneﬁt has been shown compared with
parenteral nutrition and is based on an assumption that an
early- or patient-controlled oral diet is unacceptable [ 31].
The superiority of enteral tube feeding over an early oral
diet after major abdominal surgery (including after PD),
has not been documented and the opposite might well bethe case (as outlined above). Oral nutritional supplemen-
tation post-hospital discharge seems appealing in a patient
group known to struggle to achieve dietary goals, butevidence for a beneﬁt is lacking [ 184].
Summary and
recommendationPatients should be allowed a normal diet
after surgery without restrictions. They
should be cautioned to begin carefully
and increase intake according totolerance over 3–4 days. Enteral tube
feeding should be given only on speciﬁc
indications and parenteral nutritionshould not be employed routinely
Evidence level Early diet at will: Moderate
RecommendationgradeStrong
Early and scheduled mobilisation
The relatively slow resumption of function in the stomach
and gut together with signiﬁcant surgical trauma leads to aprolonged recovery period in PD patients compared with
many other laparotomy patients even in the absence of
major complications. Extended bed rest is associated with
several unwanted effects [ 185,186]. Scientiﬁc data are
lacking, but the authors have observed the feasibility of
written instructions for patients with detailed day-to-day
targets postoperatively. This ensures autonomy and coop-eration from patients. Daily progress can be monitored with
diaries or with simple monitoring devices for patient
activity. Analgesia must be adequate not only for rest, but
also for early mobilisation.
Summary and
recommendationPatients should be mobilized actively
from the morning of the ﬁrst post-
operative day and encouraged to meet
the daily targets for mobilisation
Evidence level Very low
Recommendation
gradeStrong
Audit
Systematic audit is essential to determine clinical outcome
and to establish the successful implementation and con-tinued use of a care protocol. There are also indications that
audit per se improves clinical results through feedback
[187]. It is vital to distinguish between unsuccessful
implementation and lack of desired effect from an imple-
mented protocol if results are short of the desired quality
standards. Comparison with other centres using similarprotocols via
identical tools of registration and identical
deﬁnitions of key factors is needed.
Summary and
recommendationSystematic audit improves compliance
and clinical outcomes
Evidence level LowRecommendation
gradeStrong
Conclusion
ERAS
/C210programmes have been strongly associated with
reduced LOSH but this may not be the best indicator of the
quality of functional recovery. An awareness of goals thatimprove safety and clinical outcomes is of greater impor-
tance. Emphasis must be placed on reducing morbidity
with the introduction of standardised and appropriateenhanced recovery programmes based on best available
scientiﬁc evidence.
Multimodal ERAS programmes are complex interven-
tions that pose signiﬁcant challenges to evaluation by
conventional RCTs [ 175,188]. The most obvious of these252 World J Surg (2013) 37:240–258
123

challenges are standardisation of the intervention and a
rapidly closing window of opportunity from ethical and
practical concerns [ 189]. This may, to some extent, explain
the relative paucity of RCTs evaluating ERAS programmesand the somewhat limited effect that has been shown on
endpoints other than LOSH. In addition, interventions like
these pathways are prone to show signiﬁcant Hawthorne orTrial effects [ 190,191]. This implies that the collateral
effect on the infrastructure and management culture to
implement such a comprehensive programme will have
beneﬁcial consequences in addition to those caused by the
protocol items themselves or their synergistic effect. As hasalso been pointed out for this patient group [ 175], this is
nevertheless a beneﬁt related to the use of these pro-
grammes. For these reasons it may be argued that a ran-domised evaluation of an evidence-based ERAS protocol
against traditional care may not be the way forward. Fur-
thermore, it seems reasonable to propose that, if RCTs haveproven the beneﬁt (item by item) of two wheels, two
pedals, a frame, a chain and a handle bar, then a bicycle is
highly likely to be a valuable tool. Feasibility, however,must be ensured. Hence, multicentre and multinational
prospective validation of a uniﬁed and comprehensive
perioperative care protocol in consecutive cohorts ofpatients undergoing PD is warranted.
Conﬂict of interest The ERAS Society/C210receives an unrestricted
grant from Nutricia Clinical Care. KL, MMEC, KS, FC, MS, RWP,
KCHF, ND, MB, CHCD: Declare no conﬂicts of interests. JEdA-N
has received travel support for lectures and meetings from Nestle andFresenius-Kabi. DNL has received unrestricted research funding,travel grants and speaker’s honoraria from Baxter Healthcare,
Fresenius Kabi and BBraun. OL has served as an external Advisor to
Nutricia Clinical Care, and received travel and lecture honoraria fromNutricia, Fresenius-Kabi, BBraun, Baxter and Nestle. OL previouslyheld a patent for a preoperative carbohydrate drink formerly licensed
to Nutricia.
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