A n a e s t h e s i a fo r P a n c rea t i c

S u r ge ry
a, b
Leigh J.S. Kelliher, MBBS, BSc, FRCA, MD *, Anton Krige, MBChB, DIMC, FRCA, FFICM

KEYWORDS
 ERAS  Enhanced recovery  Fast track  Pancreaticoduodenectomy
 Whipple’s procedure  Pancreatic cancer

KEY POINTS
 Pancreatic cancer is a leading cause of cancer death globally and pancreatic resection
remains the only curative treatment option.
 Pancreatic resection is complex and is itself associated with a significant risk of morbidity
and mortality.
 Careful patient selection and optimization alongside perioperative care based on current
enhanced recovery guidance may reduce postoperative morbidity and facilitate further
oncological treatment, thereby improving long-term outcomes.
 Future efforts to improve outcomes must focus on the earlier detection of malignancy, ad-
vances in surgical and anesthetic techniques, and the development of more effective
adjuvant therapies.

INTRODUCTION

The anatomy and physiology of the pancreas and its location within the body mean
pancreatic surgery is often complicated and high risk. The most common pancreatic
surgical procedures are pancreaticoduodenectomy and distal pancreatectomy. The
indications for surgery are varied but this article will principally focus on pancreatico-
duodenectomy within the setting of pancreatic cancer.

PANCREATIC CANCER

Despite advances in treatment and improved survival times for many different types of
cancer, the prognosis for those diagnosed with pancreatic cancer remains poor. Glob-
ally there are almost half a million new cases of pancreatic cancer (mainly adenocar-
cinoma) diagnosed every year, giving an age-standardized incidence rate of 4.8 per

Declarations/conflicts of interest: I have no declarations/conflicts of interest.

a
Department of Anaesthetics, Royal Surrey County Hospital NHS Foundation Trust, Egerton
Road, Guildford, Surrey, GU2 7AS, UK; b Department of Anaesthesia and Critical Care, Royal
Blackburn Teaching Hospital, Haslingden Road, Blackburn BB2 3HH, UK
* Corresponding author.
E-mail address: lkelliher@nhs.net

Anesthesiology Clin 40 (2022) 107–117

https://doi.org/10.1016/j.anclin.2021.11.005 anesthesiology.theclinics.com
1932-2275/22/ª 2021 Elsevier Inc. All rights reserved.
108 Kelliher & Krige

100,000.1 These rates are 3 to 4 times higher in the developed world with north Amer-
ica, Europe, and Australasia topping the list. It is estimated that the overall 1-year sur-
vival for all patients diagnosed is approximately 25%, dropping to 5% at 5 years.2
Surgical removal of the primary tumor is the only curative treatment and one major
determinant of survival is the stage of cancer at presentation. This may be divided
into 4 categories—resectable, borderline resectable, locally advanced unresectable,
and metastatic.3 Only 10% to 15% of patients present with resectable disease. 5-
year survival may be as high as 25% for those whereby surgery is possible, compared
with a median survival of 6 months in those whereby it is not.2 As a result, while the
incidence of pancreatic cancer is far smaller than that of lung, breast, colon, prostate,
skin, and others it is the seventh leading cause of cancer death globally.1

PANCREATICODUODENECTOMY

Pancreaticoduodenectomy is a complex surgical procedure involving en-bloc resec-

tion of the head of the pancreas, gallbladder, duodenum, distal stomach (pylorus), and
proximal jejunum followed by reconstruction via gastrojejunostomy, hepaticojejunos-
tomy, and pancreaticojejunostomy (Fig. 1). The principle indication for this surgery is
cancer of the pancreatic head but it is also used for the treatment of other periampul-
lary cancers—duodenal and cholangiocarcinoma—as well as benign tumors, chronic
pancreatitis affecting the head of the pancreas, and neuroendocrine tumors. The pro-
cedure was pioneered in the 1930s by an American surgeon named Allen Oldfather
Whipple4 and hence is widely known as the Whipple procedure. Historically it has
been associated with significant postoperative mortality and morbidity, reported as
high as 25% and 60%, respectively, in the 1960s.5 With advances in surgical tech-
nique, perioperative care, and patient selection these figures have reduced, and the
current mortality is estimated at approximately 4% with some high-volume centers
reporting mortality as low as 1%.6,7 Postoperative morbidity remains a significant
issue with the principal problems being surgical site infections, pulmonary complica-
tions, anastomotic leaks, fistulas and delayed gastric emptying.8 In an attempt to
reduce some of these complications, alternatives to the classical pancreaticoduode-
nectomy have been developed. Primary among these is the pylorus-preserving

Fig. 1. The anatomy of the classical pancreaticoduodenectomy (Whipple procedure). (A)

Anatomy resected (shaded area). (B) Reconstruction. (From Gall, T. M. H., Tsakok, M., Wasan,
H., & Jiao, L. R. (2015). Pancreatic cancer: current management and treatment strategies.
Postgraduate Medical Journal, 91(1080), 601–607. https://doi.org/10.1136/postgradmedj-
2014-133222)
 Anaesthesia for Pancreatic Surgery 109

pancreaticoduodenectomy (PPPD) (Fig. 2) whereby the distal stomach is not

resected. Proponents of this approach assert it is associated with shorter operative
times and less intraoperative bleeding as well as better long-term gastrointestinal
function, fewer peptic ulcers, and lower incidence of dumping syndrome9 but critics
point to its association with delayed postoperative gastric emptying and that, as the
resection is less radical, the chance of incomplete tumor removal/positive margins
is increased.10 A recent Cochrane review of comparing pancreaticoduodenectomy
with PPPD found no differences in mortality, morbidity or survival between the 2 pro-
cedures although the authors also commented on the relatively poor quality of avail-
able data.11

OPEN VERSUS MINIMALLY INVASIVE SURGERY

Classically, pancreaticoduodenectomy is an open procedure. A variety of incisions are

used including chevron, straight transverse, and curved transverse and with no cur-
rent evidence/consensus for the superiority of one over another the choice often de-
pends on surgical preference. In common with many other surgical procedures,
minimally invasive techniques (both laparoscopic and robotically assisted) have
been developed with the goal of reducing postoperative morbidity and recovery times.
Several meta-analyses have examined the evidence comparing minimally invasive
with open pancreaticoduodenectomy the results of which indicate that while the mini-
mally invasive approach may be associated with less intraoperative blood loss, lower
transfusion rates, and shorter hospital stays, there is no difference in major morbidity
or mortality and operative times are longer.12–14 All point to the need for further high-
quality evidence. Currently, the use of minimally invasive pancreaticoduodenectomy
depends on the available surgical expertise and careful patient selection.

ADJUVANT/NEOADJUVANT CHEMORADIOTHERAPY

With high rates of early cancer recurrence and poor one- and 5-year survival following
pancreaticoduodenectomy alone, the use of adjuvant chemotherapy  radiotherapy
to improve outcomes has been a subject of investigation over the past 4 decades.

Fig. 2. The anatomy of the pylorus-preserving pancreaticoduodenectomy (PPPD). (A) Anat-

omy resected (shaded area). (B) Reconstruction. (From Gall, T. M. H., Tsakok, M., Wasan, H.,
& Jiao, L. R. (2015). Pancreatic cancer: current management and treatment strategies. Post-
graduate Medical Journal, 91(1080), 601–607. https://doi.org/10.1136/postgradmedj-2014-
133222)
110 Kelliher & Krige

By the late 1980s evidence was emerging that surgery followed by adjuvant chemo-
radiotherapy with 5-Fluorouracil led to improved survival versus surgery alone.15
Over the decades as there has been a great deal of research into finding the optimal
chemotherapeutic agents and treatment protocol and at this current time practice
varies across the globe. Some centers advocate the use of combined radiotherapy
and chemotherapy, whereas others favor chemotherapy alone as first-line adjuvant
treatment following pancreaticoduodenectomy. Agents commonly utilized are gemci-
tabine, S1 (tegafur/gimeracil/oteracil), FOLFIRINOX (folinic acid, 5-fluorouracil, irinote-
can, oxaliplatin), or combinations of these, all of which have been shown to improve
survival.16
Despite the demonstrable survival benefits associated with adjuvant therapy, a sig-
nificant proportion of patients are not eligible/unable to receive it. Approximately 25%
of patients are found to have unresectable cancer (either due to local invasion or
metastasis) at the time of surgery17 and do not, therefore, receive adjuvant therapy.
Accurate staging is essential and this statistical just illustrates how challenging it
can be. Patients suspected of having pancreatic cancer first undergo investigation
in the form of CT or MRI imaging with resectability being assessed via the size and
invasiveness of the primary tumor and whether or not metastases/lymphatic spread
is present. The sensitivity of CT/MRI for detecting micrometastases is poor and
many centers utilize FDG PET scanning to enhance this. While more invasive, the
development of endoscopic ultrasound (EUS) assessment has further enhanced the
accuracy of diagnosis and staging, particularly in cases whereby a tissue diagnosis
is required as EUS facilitates the sampling of the tumor via fine-needle aspiration
(FNA). Even when the resectability of the tumor is predicted accurately, 20% of pa-
tients undergoing a successful resection do not recover adequately from the surgery
to commence adjuvant therapy. This has led researchers to examine the role of neo-
adjuvant therapy (as opposed to the traditional approach of surgery first) not only as a
way of ensuring more patients are able to receive chemo/radiotherapy but also for
potentially reducing the number of patients found to be inoperable at the time of sur-
gery, increasing the chance of clear resection margins and preventing early cancer
recurrence. To date the benefits of neoadjuvant therapy remain hypothetical with
most studies finding no overall survival benefit;16,18,19 however, the search for the
optimal protocol continues and several RCT’s compare neoadjuvant therapy with
surgery-first are ongoing.

PREOPERATIVE CONSIDERATIONS

The preoperative issues encountered when treating these patients are many and de-
cision making can be extremely complex. As discussed, pancreaticoduodenectomy is
major abdominal surgery associated with a significant risk of morbidity and mortality.
Most of the patients present with obstructive jaundice and will have marked physio-
logic derangement. In addition, they are often elderly, cachectic, immunosuppressed,
and with poor nutritional status. Anemia and diabetes are common and with
advancing age come many other chronic comorbidities. The emotional impact of
this diagnosis must not be underestimated either—many patients will require coun-
seling/treatment of anxiety. Management is based on staging and given the prognosis
without surgery is so dismal, it is essential that this is done as accurately as possible.
Finally, for patients deemed to have resectable disease, the time between diagnosis
and surgery is critical, meaning the time-frame for preoperative assessment, coun-
seling, risk-stratification, and optimization is limited. A multi-disciplinary team
approach comprising experienced and expert health care professionals is essential.
 Anaesthesia for Pancreatic Surgery 111

RISK STRATIFICATION

Given the high-risk nature of the surgery and patient population, many centers choose
to assess patients’ cardiovascular, respiratory, and skeletal muscle systems with car-
diopulmonary exercise testing (CPET) in addition to routine preoperative tests. CPET
variables have been shown to correlate with adverse postoperative outcomes
following a variety of noncardiopulmonary surgeries, including pancreaticoduodenec-
tomy20,21 and it is used widely for risk stratification and to inform decision-making.

NUTRITION

Perioperative malnutrition is common in patients with pancreaticoduodenectomy and

is associated with a higher incidence of postoperative complications.22 Patients nutri-
tional status should be assessed preoperatively and those found to be significantly
malnourished should receive supplementation to increase calorie and protein intake
and replace minerals and vitamins either orally (via sip feeds) or enterally (via tube
feeds). Equally, postoperative nutrition should be supplemented orally or enterally.
The routine use of parenteral nutrition has not been shown to be beneficial and is asso-
ciated with complications, and therefore, should be avoided.23,24

PREOPERATIVE BILIARY DRAINAGE

For many patients, the first symptom of pancreatic cancer is jaundice. Compression
of the common bile duct by tumor in the head of the pancreas causes obstructive
jaundice which in turn can result in renal impairment, liver dysfunction, cardiac
dysfunction, immune dysfunction, and abnormalities of blood clotting.25 Drainage
of the biliary system either percutaneously or endoscopically will correct the
obstruction and ameliorate these risks but is associated with procedure-specific
complications including hemorrhage, sepsis, and localized inflammation26 which
may delay, or worsen, overall outcome following pancreaticoduodenectomy. A sys-
tematic review examining the practice of preoperative biliary drainage found insuffi-
cient evidence to support or refute its use, with the authors concluding that routine
use of preoperative biliary drainage should be avoided.25 Current ERAS guidelines
indicate that it may still be considered for patients with serum bilirubin greater
than 250 mmol/L.24

ERAS RECOMMENDATIONS

Originating in colorectal surgery with the purpose of improving postoperative out-

comes via minimizing the stress of anesthesia and surgery, fast-track programs
have shown to be beneficial for a variety of surgical procedures.27–30 The Enhanced
Recovery After Surgery (ERAS) Society produced consensus guidelines for the periop-
erative care of patients with pancreaticoduodenectomy in 2013.24 These are summa-
rized in Table 1. A number of systematic reviews have examined the evidence for the
use of fast-track programs in pancreaticoduodenectomy concluding that it is feasible,
safe, and may be associated with reduced length of hospital stay and postoperative
morbidity.31–35 However, the majority of the evidence comes from retrospective
cohort studies with no RCTs identified. A study from 2019 attempted to identify factors
associated with early discharge following pancreaticoduodenectomy by retrospec-
tively examining the records of more than 10,000 patients from the ACS-NSQIP data-
base. They found that early discharge (LOS 5 days or less) was significantly associated
with younger age, absence of obesity, COPD and hypertension, neoadjuvant chemo-
therapy, shorter operative time, and minimally invasive surgery. Patients that received
112 Kelliher & Krige

Table 1
ERAS society perioperative care recommendations for pancreaticoduodenectomy

Recommendation Strength
Routine perioperative counseling Strong
Avoid routine preoperative biliary drainage if serum bilirubin <250 mmol/L Weak
Stop smoking and alcohol consumption for 1 mo before surgery Strong
Oral or enteral preoperative nutritional supplements only for patients who Weak
are significantly malnourished
Consider immuno-nutrition 5–7 d preoperatively Weak
Avoid bowel preparation Strong
Preoperative oral carbohydrate load – except in diabetics Strong
Avoid preoperative sedatives Weak
LMWH continued for 4 wk postoperatively Strong
Routine antimicrobial prophylaxis Strong
Epidural analgesia (open surgery) Weak
Multimodal approach to PONV prevention Strong
Avoid hypothermia Strong
Postoperative glycaemic control Strong
Aim for near-zero fluid balance with goal-directed fluid therapy using Strong
balanced crystalloid solution
Early removal of surgical drains (72 h) Strong
Early removal of urinary catheter (48 h) Strong
Consider artificial nutrition in patients with delayed gastric emptying Strong
Allow early oral intake, building to normal diet over 3–4 d. Strong
Early and scheduled mobilization from the morning of the first Strong
postoperative day
Audit compliance and outcomes Strong

From Lassen, K., Coolsen, M. M. E., Slim, K., Carli, F., de Aguilar-Nascimento, J. E., Schäfer, M., Parks,
R. W., Fearon, K. C. H., Lobo, D. N., Demartines, N., Braga, M., Ljungqvist, O., & Dejong, C. H. C.
(2012). Guidelines for Perioperative Care for Pancreaticoduodenectomy: Enhanced Recovery After
Surgery (ERAS) Society Recommendations. World Journal of Surgery, 37(2), 240–258. https://doi.
org/10.1007/s00268-012-1771-1.

an epidural, jejunostomy tube, abdominal drain, or who required adhesiolysis were

significantly less likely to be discharged early.36 A number of these factors are poten-
tially modifiable and may indicate areas of focus for future enhanced recovery
programs.

ANESTHETIC TECHNIQUE

Pancreaticoduodenectomy is a high-risk intrabdominal surgery and the anesthetic

technique should reflect this. Tracheal intubation, wide bore peripheral and central
iv access, invasive blood pressure monitoring, regular blood gas sampling, active
warming, glycemic control, VTE, and antimicrobial prophylaxis are all standard.
Massive hemorrhage is among the potential intraoperative complications and should
be prepared for. The use of cardiac output monitoring to guide fluid and vasopressor
management has been shown to reduce complications in major gastrointestinal sur-
gery and should be considered.36 Depth of anesthesia monitoring minimizing effective
dosing of anesthetic agent, perhaps making hemodynamic management simpler while
 Anaesthesia for Pancreatic Surgery 113

reducing the incidence of postoperative delirium both of which may be of benefit in this
high-risk population.37,38
Fluid management and analgesia are 2 particularly challenging aspects of anes-
thetic care in this setting. Prolonged surgery, inflammatory mediators, anesthesia/
epidural induced hypotension, and blood loss can all complicate the estimation of fluid
requirements. Fluid overload is associated with increased morbidity following pan-
creaticoduodenectomy39 and ERAS guidelines recommend targeting a near-zero fluid
balance using a balanced crystalloid solution and cardiac output monitoring to help
guide fluid bolus administration.24
Analgesic modality will depend on the surgical approach adopted and local exper-
tise and practice. For open surgery, current ERAS guidelines advocate the use of
thoracic epidural analgesia24 and while an effective, well-managed epidural offers
excellent resting and dynamic pain relief epidural analgesia can be associated with hy-
potension and fluid overload40 and failure rates as high as 30% have been reported.41
They are not recommended in the context of minimally invasive surgery. There are
many alternatives that might be considered including the use of local anesthetic
wound catheters, abdominal field blocks, intrathecal opioids, lidocaine infusions,
and of course parenteral opioids. There is no consensus evidence for any particular
technique/combination and analgesic regimens should be tailored to fit with local
expertise and surgical practice. ERAS recommends in general that analgesia should
be multimodal, opioid-sparing with the aim of providing effective pain relief, allowing
early mobilization while minimizing the risks of ileus, PONV, drowsiness, hallucination,
and respiratory depression.

POSTOPERATIVE CARE

The high-risk nature of this surgery alongside the frequent occurrence of complica-
tions necessitates that these patients are managed postoperatively in an ICU/HDU
setting. Alongside the general risks that come with major intraabdominal surgery
such as bleeding, sepsis, pulmonary complications, ileus, wound infection, and
venous thromboembolism are some procedure-specific complications that frequently
arise.

DELAYED GASTRIC EMPTYING

Occurring in approximately 10% to 25%42 delayed gastric emptying causes signifi-

cant discomfort for patients, prolongs recovery time, and prevents a return to the
normal oral diet. An underlying cause such as a collection or anastomotic leak must
be excluded but most delayed gastric emptying resolves with time.6 A proportion of
patients will require naso-gastric drainage and nutritional supplementation. Clear ev-
idence to support the prophylactic use of prokinetic agents such as metoclopramide
to reduce the incidence and duration of DGE has yet to emerge.

PANCREATIC LEAK/FISTULA

The incidence of pancreatic leak (anastomotic breakdown of the pancreaticojejunos-

tomy and leakage of pancreatic secretions) is estimated between 8% and 13%.43
Diagnosis may be confirmed by the presence of amylase (>100 IU/L) in the perianas-
tomotic drain. Most leaks may be managed conservatively by keeping the drain in
place until the leak stops.6,43 However, a proportion may develop abscess formation
and sepsis, pseudo-aneurysm, or a major gastrointestinal hemorrhage. Pancreatic
leak-associated mortality may be as high as 5%.44
114 Kelliher & Krige

FUTURE DIRECTIONS

Pancreatic cancer remains a challenge to cure due to often late presentation and inva-
siveness of treatment. Surgery is the only curative treatment, but it is associated with
significant morbidity and mortality and only a small proportion of cancers are resect-
able. Future efforts must be directed toward increasing this number, either by earlier
detection and screening or by developing more effective neoadjuvant treatment.

Fig. 3. The cancer journey for 1000 patients diagnosed with pancreatic cancer and areas
which may lead to improvement in oncological outcomes.
 Anaesthesia for Pancreatic Surgery 115

Prognosis is poor even following successful surgery and with morbidity rates of 20%
to 40% a significant number of patients never recover adequately enough to proceed
with further treatment. Efforts to reduce postoperative morbidity through the
continuing development of minimally invasive techniques and perioperative care path-
ways are essential (Fig. 3).

CLINICS CARE POINTS

 Perioperative malnutrition is common in patients with pancreaticoduodenectomy and

associated with postoperative morbidity. All patients should be routinely screened and
those found to be significantly malnourished, treated with oral or enteral supplementation.
The routine use of parenteral nutritional support should be avoided.
 Perioperative fluid management can be extremely challenging in this group of patients and
is complicated by prolonged surgery, the magnitude of the inflammatory response,
anesthesia/epidural-induced hypotension, and blood loss. A tailored approach using a
balanced crystalloid solution and cardiac output monitoring to guide fluid boluses is
recommended with the goal of maintaining adequate end-organ perfusion while avoiding
fluid overload, targeting a near-zero fluid balance.
 Delayed-gastric emptying occurs frequently following pancreaticoduodenectomy and will
often resolve with conservative management and time. It is important to exclude
significant underlying pathology such as an abdominal collection or anastomotic leak

DISCLOSURE

The authors have no conflicts of interest to disclose.

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