Anaesthesia For Pancreatic Surgery
Anaesthesia For Pancreatic Surgery
Anaesthesia For Pancreatic Surgery
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
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
Anaesthesia for Pancreatic Surgery 109
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.
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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.
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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
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
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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.
ANESTHETIC TECHNIQUE
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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.
PANCREATIC LEAK/FISTULA
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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.
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
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).
DISCLOSURE
REFERENCES
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
116 Kelliher & Krige
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
Anaesthesia for Pancreatic Surgery 117
29. Zhu S, Qian W, Jiang C, et al. Enhanced recovery after surgery for hip and knee
arthroplasty: a systematic review and meta-analysis. Postgrad Med J 2017;
93(1106):736–42.
30. Scheib SA, Thomassee M, Kenner JL. Enhanced Recovery after Surgery in Gy-
necology: A Review of the Literature. J Minim Invasive Gynecol 2019;26(2):
327–43.
31. Spelt L, Ansari D, Sturesson C, et al. Fast-track programmes for hepatopancre-
atic resections: where do we stand? HPB (Oxford) 2011;13(12):833–8.
32. Hall TC, Dennison AR, Bilku DK, et al. Enhanced recovery programmes in hepa-
tobiliary and pancreatic surgery: a systematic review. Ann R Coll Surg Engl 2012;
94(5):318–26.
33. Coolsen MME, van Dam RM, van der Wilt AA, et al. Systematic Review and Meta-
analysis of Enhanced Recovery After Pancreatic Surgery with Particular
Emphasis on Pancreaticoduodenectomies. World J Surg 2013;37:1909–18.
34. Kagedan DJ, Ahmed M, Devitt KS, et al. Enhanced recovery after pancreatic sur-
gery: a systematic review of the evidence. HPB (Oxford) 2015;17(1):11–6.
35. Mahvi DA, Pak LM, Bose SK, et al. Fast-Track Pancreaticoduodenectomy: Fac-
tors Associated with Early Discharge. World J Surg 2019;43(5):1332–41.
36. Pearse RM, Harrison DA, MacDonald N, et al. Effect of a perioperative, cardiac
output-guided hemodynamic therapy algorithm on outcomes following major
gastrointestinal surgery: a randomized clinical trial and systematic review.
JAMA 2014;311(21):2181–90 [published correction appears in JAMA. 2014 Oct
8;312(14):1473].
37. Punjasawadwong Y, Phongchiewboon A, Bunchungmongkol N. Bispectral index
for improving anaesthetic delivery and postoperative recovery. Cochrane Data-
base Syst Rev 2014;2014(6):CD003843.
38. Radtke FM, Franck M, Lendner J, et al. Monitoring depth of anaesthesia in a ran-
domized trial decreases the rate of postoperative delirium but not postoperative
cognitive dysfunction. Br J Anaesth 2013;110(Suppl 1):i98–105.
39. Wright GP, Koehler TJ, Davis AT, et al. The drowning whipple: Perioperative fluid
balance and outcomes following pancreaticoduodenectomy. J Surg Oncol 2014;
110:407–11.
40. Pratt WB, Steinbrook RA, Maithel SK, et al. Epidural analgesia for pancreatoduo-
denectomy: a critical appraisal. J Gastrointest Surg 2008;12(7):1207–20. https://
doi.org/10.1007/s11605-008-0467-1.
41. Hermanides J, Hollmann MW, Stevens MF, et al. Failed epidural: causes and
management. Br J Anaesth 2012;109(Issue 2):144–54.
42. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after
pancreatic surgery: a suggested definition by the International Study Group of
Pancreatic Surgery (ISGPS). Surgery 2007;142:761–8.
43. Cullen J, Sarr M, Ilstrup D. Pancreatic anastomotic leak after pancreaticoduode-
nectomy: Incidence, significance, and management. Am J Surg 1994;168(4):
295–8.
44. American Gastroenterological Association. American Gastroenterological Associ-
ation medical position statement: epidemiology, diagnosis, and treatment of
pancreatic ductal adenocarcinoma. Gastroenterology 1999;117:1463–84.
Descargado para Anonymous User (n/a) en CES University de ClinicalKey.es por Elsevier en mayo 09, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.