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Client Assessment Form

Client Initials: M.F.

Client Room Number: 274

Client Age: 46

Sex: Female

Admission Date: 2/8/2015

Code Status: Full

Admitting Diagnosis: pancreatitis

Surgical Procedure: Cholecystectomy Date of Surgery: pending

Allergies/Type of Reaction: None reported.

Additional information regarding diagnosis: Patient reports having previous bouts with

pancreatitis and associated abdominal pain.

Social History

Native Language: English Marital Status: Single Religious Background: Christian

Culture: N/A Special Needs R/T Culture: N/A Social Support System: Husband

Whom do you live with: Client lives with husband Caregiver at home: Yes

If so who: Husband Caregiver have adequate support: Yes Tobacco Use: No

Alcohol/Drug Use: No When was your last drink/use: N/A

Frequency: N/A How many years: N/A

Medical/Surgical History

Medical Year Surgical Year C-section 1994

Erickson Developmental Stage

According to age: Generativity vs. Stagnation

Supporting Data: Client is a wife and mother. She needs to recover and return to a productive

family life.


Has present or past illnesses affected this level: Client has had previous bouts of abdominal pain

related to pancreatitis. She has been hospitalized and managed her pain; however, client wishes

to have gallbladder removed at this time to avoid further exacerbation.

Diet

Current Diet: Liquids only. Order changed to NPO during shift.

Rationale: Client was nauseated and needed GI rest, therefore, liquids only. NPO status upon

learning cholecystectomy was pending due to need to prepare for anesthesia.

Fluid/Food Restrictions: Client is on restrictions. Expectation is for the client to progress from

NPO to liquids and soft foods after surgery.

Evaluation: 0715: Client consumed 1 cup of hot tea

0943: Client put on NPO

1140: Client still compliant with NPO

1436: Client still compliant with NPO

Routine Medications Ordered in Hospital

Drug Name

(Trade and Generic)

Dose/Route Frequency Reason for Taking What are the nursing

implications?

Pantoprazole sodium 40mg/IV daily Decrease gastric Take w/o regard to meals. (Protonix inj.) secretions Report any rash, dyspepsia

or bowel changes. Monitor

for GI irritation.

Potassium chloride in 1000@100mL/hr Q10H Treats Monitor ECG, fluids, K+.

Lactated Ringer’s & /IV hypokalemia Report confusion, weakness,

5% dextrose N/V/D and I&Os.

Odansetron (Zofran) 10mg/PO PRN Q4H Antiemetic Monitor liver function tests. Report dizziness,

constipation, difficulty

breathing.

Hydromorphone 1mg/IV PRN Q6H Pain relief Monitor breathing. Do not

(Dilaudid) drive or drink alcohol. May cause sedation, impaired

breathing, anxiety,

constipation.

Acetaminophen/Tylenol 650mg/PO PRN Q4H Fever >101 Assess client’s temperature

mailto:1000@100mL


Significant Laboratory Values

Lab Test Normal

Range

Labs

Clinical

Rationale Nursing Care/Client

Teaching

Potassium 3.5-5.0 3.1 Low due to liquid Administer potassium diet. Vomiting also as ordered.

leads to

hypokalemia.

Calcium 8.5-10.5 8.2 Low due to patient Administer

vomiting. supplements if

ordered.

BUN 10-20 6 Low value can Monitor IV fluids and

indicate kidneys not intake and output.

functioning

optimally.

AST 5-50 104 Both AST/ALT are Monitor lab results.

too high. These are Look for improvement

produced in liver in level after surgery.

and would be

expected to be high

in pt. experiencing

liver or gallbladder

disease. ALT 5-40 335 See above. See above.

Alkaline 30-115 159 High value can Monitor labs. Look for

phosphate indicate liver improvement in level

disease or presence after surgery.

of gallstones.. Total bilirubin .2-1.2 2.0 High value indicates Monitor labs. Look for

liver not functioning improvement in level

properly. This can after surgery.

occur with the

presence of

gallstones.

Albumin 3.5-5.0 3.1 This level indicates Administer IV

nutritional deficits. replenishment

This is most likely solutions as ordered.

due to pt. vomiting Monitor labs. Albumin

and being only level should normalize

liquid only diet. after surgery and with

implementation on

better nutrition.


Diagnostic Test

Specific Test Date Result Clinical Significance Client Teaching/

Nursing Care

Endoscopy 2/9/15 No blockage noted, inflammation present

Monitor pain Pain Management

SafetyUltrasound of 2/9/15 Gallstones present Surgery needed Diet/Lifestyle change

gallbladder Medication compliance

Discharge Planning

Knowledge Deficits: surgical procedure, self-care, medications

Specific Needs R/T Identified Information (wound care, diet, medications, mobility, etc.): Medications, Mobility, and

Self-Care

Do you currently use any community resources?: No

Home Health Care: No

Sitters: No

Hospice: No

Community/Church: No

Meals on Wheels: No

Home Health Aid: No

Adult Day Care: No

Discharge Planning

Who will assist you after discharge: Husband

Where will you go after discharge?: Home

Will you need help with any of the following?:

Feeding: Yes

Grooming: No

Bathing: No

Toileting: No

Dressing: No

Walking: No

Moving in Bed: No

Anticipated discharge needs?:

Equipment: No

Teaching: Yes

Social Services: No

Support Groups: No

Financial Resources: Yes

Assistance at Home: Yes

PT: No


Environmental Assessment:

Running Water: Yes

Electricity: Yes

Air Conditioning: Yes

Fans: Yes

Stairs: No

Refrigerator: Yes

Vital Signs

Time Temp Pulse Resp. BP 02 Pain

0730 98.4 – Oral 74 20 134/77 97% RA 6 out 10

1130 98.3 – Oral 72 12 127/74 96% RA 2 out 10

1530 98.2 – Oral 87 12 128/76 96% RA 1out 10

Intake and Output

Time Intake Type Output Type

0730 236 mL tea

1145 1000ml IV-LR

Assistive Equipment in Use

List all assistive equipment in use:

IV

Safety Precautions in Use

Safety precautions in use:

Side rails up times three.

Bed in lowest position

Call light in reach.

Personal belongings in reach.

Client is not in isolation.

Restraints are not in use.

Physical Assessment

Completes all assessments on all body systems as appropriate: 0700

a) Cognitive/Perception/Neurological: A&O x 3, normocephalic, atraumatic, Fall Risk Assessment

b) Cardiovascular: Heart sounds S1, S2 loudest, regular rate & rhythm, no peripheral edema

c) Respiratory/Pulmonary: Breath sounds equal and bilateral, RR=20 d) Integumentary: skin intact, no wounds noted, skin warm & dry, IV access L FA: no redness or infiltration


e) Gastrointestinal : Full liquids only. Bowel sounds active in all 4 quadrants. Abdomen soft.

f) Genitourinary: No assessment

g) Musculoskeletal : No tenderness in extremities. Normal ROM. No cyanosis or edema.


Problem

Intervention

Evaluation

Safety Bed in lowest/locked position. Side rails up x2. Call button/personal belongings within reach.

0700 Pt. is safe. VS: 98.4-74-20. BP 134/77. 97% RA. Pain 6/10. SK CCSN2

Pain – Pt. reports pain of 6/10.

Pt. describes pain as sharp and shooting in abdomen. Repositioning helped temporarily. Fall risk assessment performed. Pt. given hydromorphone (Dilaudid) 1mg/IV.

0710 Pt. given pain med and assessed. VS WNL. Pt. reports pain 4/10. Pt. is low risk for falls. Pt. told to call for assist. if drowsy due to med. SK CCSN2

Respiratory/CV- Pt. denies difficulty breathing.

Breathing assessed. Cardiovascular assessed. 0710 Breathing is regular and bilaterally clear. Heart sounds S1,S2 loudest. Reg. rhythm &rate. No peripheral edema. SK CCSN2

Neuro/Musculoskeletal – Pt. awake & oriented x3. Follows commands and moves all extremities.

Pt. reassured. Pt. had no questions concerning plan of care or medications. Performed fall risk assessment.

0710 Pt. neuro intact. Pt. verbalized will call if assistance is needed. Pt. is low risk for falls. SK CCSN2

GI – No bowel movement since 2/8/15.

Assessed bowel sounds. Sounds present in all four quadrants.

0710 Pt. denies constipation, Continue with full liquid diet. Pt. will notify if bowel movement occurs. SK CCSN2

Integumentary Skin assessment performed. 0710 Skin intact, no wounds noted. Skin warm & dry. IV access L FA, no redness or infiltration. SK CCSN2

Safety Pt. checked and resting comfortably. Bed in lowest/locked position. Side rails up x2. Call button/personal belongings within reach.

0943 Pt. is safe. SK CCSN2

Pain Pain assessed. Patient reported pain 1/10. 0943 Patient reports no severe pain. SK CCSN2

GI – Order for NPO Patient told status is now NPO due to pending procedure.

0943 Patient verbalized understanding of NPO status. SK CCSN2

Safety Pt. checked. Pt. resting in bed in semi- Fowler’s. States no pain. Bed in lowest/locked position. Side rails up x2. Call button /personal belongings within reach. Pt. reports compliance with NPO.

1140 Pt. is safe. Pt. reports nausea. SK CCSN2

Medication Replaced potassium chloride/Lactated Ringer’s. Given Zofran 4mg IV for nausea.

1140 Meds given. Patient has no adverse reactions. Pt. told to call if nausea persists. Pt. reports pain 1/10. SK CCSN2

Safety Pt. checked. Pt. resting in bed in semi- Fowler’s. States no pain. Bed in lowest/locked

1436 Pt. is safe. Reports pain 1/10. Husband at bedside.


position. Side rails up x2. Call button /personal belongings within reach. Pt. reports compliance with NPO.

SK CCSN2

Mucous membranes - dry

Patient assessed due to NPO status and complaint of dry mouth. Pt. told to swish water in mouth but not to swallow to help relieve dry mouth.

1436 Pt. verbalized understanding. Husband at bedside. SK CCSN 2

Patient Education – deficient knowledge

Pt. provided with educational materials explaining post-op diet and exercise and disease process. Husband involved in education.

1436 Pt. verbalized examples of exercises and healthy foods and a plan for implementation upon discharge. Pt. verbalized lifestyle changes to be made. Husband at bedside. SK CCSN 2

Rm# 274 DOC: 2/11/15

VS: BP 134/77 Temp. 98.4 Pulse 74 RR 20 Weight:75kg

Patient Demographics

Age: 46 Sex: F

Medical Dx:pancreatitis

Past Med & Surg Hx: C- section

Diag Tests:

Endoscopy

Ultrasound of gallbladder

Diet: Full liquid then NPO

Activity: as tolerated

Psychosocial: Married with

family support

Patient Support Data Med Dx: pancreatitis due to gallstones

Hx: Patient reports

having experienced this type of pain frequently

over the last 2 years

Meds:

Acetaminophen 650mg PO PRN Q4H Hydromorphone 1mg IV PRN Q6H Maslow’s:Physiologic

#1 Nursing Dx: Acute abdominal pain r/t gallstones AEB patient

complaint of pain 6/10.

Pt Goal: Pt. to state pain less than 3/10 by end of shift.

Nursing Interventions: 1. Assess pt. pain using scale of 1-10. Rationale: Using an evidence- based pain scale is a reliable and valid method for tracking pain. 2. Administer pain meds routinely. Rationale: Pharmacological interventions are first-line approaches to managing pain. 3. Reposition pt. as needed for comfort. Rationale: Supporting use of non-pharmacological pain management methods can help to control

pain and restore client’s sense of self-control (Pasero, 2014).

Eval of Pt Goal: Goal met.

Pt. reported pain of 1/10 by

end of shift.

Routine Meds

Pantoprazole 40mg IV daily

Potassium chloride 5meq/Dextrose

Lactated Ringer’s 1000@ 100mL/hr

Q10H

PRN Meds

Acetaminophen 650mg PO PRN Q4H Hydromorphone 1mg IV PRNQ6H

Labs

K+: 3.1

Ca+:8.2

BUN:6

SGOT (AST): 104

SGPT (ALT): 335

Alk Phosphate: 159

T. Bilirubin: 2/0

Albumin: 3.1


Hx: no history of falls

Meds: Hydromorphone

Maslow’s:Safety

Patient Support Data

Med Dx: pancreatitis due to gallstones

Hx: Patient is NPO due to impending surgery Meds: Lactated

Ringer’s

Maslow’s:Physiological

#2 Nursing Dx: Risk for falls r/t use of pain medication.

Pt Goal: Patient will remain free from falls throughout shift.

Nursing Interventions: 1. Maintain bed in lowest and locked position with the handrails up x2. Rationale: This provides the safest positioning of the client’s bed and

helps deter falls. 2. Complete a fall risk assessment. Rationale: This gives staff a baseline

of the client’s functional abilities.

3. Evaluate client medications to determine whether meds will increase risk of falling. Rationale: Client will need education on medication side effects and safety to avoid falls (Greenberg, 2014).

#3 Nursing Dx: Risk for deficient fluid volume r/t decreased fluid

intake.

Pt Goal: Patient will maintain moist tongue and mucous

membranes and weight WNL.

Nursing Interventions:

1. Hydrate the patient with ordered IV isotonic solution. Rationale: Isotonic fluids allow replacement of intravascular volume.

2. Observe for dry tongue and mucous membranes once every shift or

upon pt. complaint. Rationale: These are signs of decreased body

fluids.

3. Weigh client daily and watch for sudden decreases. Rationale: Body

weight change of 3% body weight is defined as dehydration (Dirkes, 2014).

Eval of Pt Goal: Goal

met. Patient had no falls

during the shift.

Eval of Pt Goal: Goal is

ongoing. Patient will be

monitored carefully

regarding new NPO status.


Hx: Pt. on liquid diet only due to GI upset; K+:3.1, Ca+: 8.2 Meds: Potassium chloride

5meq/Dextrose Lactated Ringer’s

Maslow’s: Physiological

#4 Nursing Dx: Imbalanced nutrition: less than requirements r/t

inadequate dietary intake AEB pt. report and by lab values. Pt Goal: Pt. albumin and electrolyte levels will improve by next blood draw.

Nursing Interventions: 1. Nurse will educate pt. about and implement liquid diet once per shift. Rationale: 2. Nurse will administer antiemetic as needed before liquid intake. Rationale: The presence of nausea or pain decreases appetite/intake.

3. Nurse will note lab test results as available: serum albumin, serum total protein, hemoglobin, hematocrit and electrolytes. Rationale:

Administer potassium supplement and/or electrolytes as ordered to

increase nutritional status. (Ackley, 2014).


partially met. Changed to

NPO in preparation for

surgery. Pt. continued to

receive K+ & electrolytes.

Next blood draw results not

avail. during shift.

Patient Support Data

Med Dx: pancreatitis

Hx: Pt. has previous

admissions for

pancreatitis.

Maslow’s:

Physiological/Safety

#5 Nursing Dx: Deficient knowledge r/t lack of understanding of

disease process. Pt Goal: Communicate desire to understand disease state and need for treatment.

Nursing Interventions: 1. Consider pt.’s ability & readiness to learn throughout shift . Rationale: Learning readiness changes over time based on situational

and physical challenges.

2. Assess personal context and meaning of illness. Rationale: Improved symptom management is a result of client-focused interventions that centered on needs and meaning and perspective of the illness.

3. Assess for cultural/ethnic self-care practices. Rationale: Home remedies and diet may interact with meds and treatments (Olinzock & Bloom, 2014).


met. Pt. verbalized

lifestyle changes to be

made.


Hx: Pt. reports experiencing this same discomfort before.

Maslow’s:

Physiological/Safety

#6 Nursing Dx: Ineffective health maintenance r/t deficient

knowledge concerning diet and activity.

Pt Goal: Pt. will verbalize understanding of diet and activities of health promotion.

Nursing Interventions:

1. Provide pt. with educational materials regarding diet and exercise at discharge. Rationale: The use of materials tailored to the client has a strong effect on dietary behavior. 2. Encourage pt. to establish a regular routine for exercise at discharge. Rationale: Clients who establish a regular routine for exercise are more

likely to be compliant over time.

3. Discuss with pt. and husband realistic goals for change in health

maintenance at discharge. Rationale: Involving family in care increases

success of a client (Bloom & Olinzock, 2014).


met. Pt. verbalized

examples of exercises and

healthy foods and a plan

for implementation upon

discharge.

References

Ackley, B., (2014). Imbalanced nutrition: less than body requirements. In Nursing diagnosis handbook: An

evidence-based guide to planning care (10th ed., pp. 558-563). Maryland Heights, MO: Mosby

Elsevier.

Bloom, K. & Olinzock, B., (2014). Ineffective health maintenance. In Nursing diagnosis handbook: An

evidence-based guide to planning care (10th ed., pp. 412-415). Maryland Heights, MO: Mosby

Elsevier.

Bouwense, S., Ali, U., ten Broek, R. ., Issa, Y., van Eijck, C. H., Wilder-Smith, O. H., & van Goor, H. (2013,

September 9). Altered central pain processing after pancreatic surgery for chronic pancreatitis.

British Journal of Surgery, 100, 1797-1804. doi:10.1002/bjs.9322 Retrieved from PubMed.

Dirkes, S., (2014). Deficient fluid volume. In Nursing diagnosis handbook: An evidence-based guide to

planning care (10th ed., pp. 365-369). Maryland Heights, MO: Mosby Elsevier.

Greenberg,S., (2014). Risk for falls. In Nursing diagnosis handbook: An evidence-based guide to planning

care (10th ed., pp. 332-337). Maryland Heights, MO: Mosby Elsevier.

Olinzock, B. & Bloom, K., (2014). Deficient knowledge. In Nursing diagnosis handbook: An evidence-based

guide to planning care (10th ed., pp. 504-507). Maryland Heights, MO: Mosby Elsevier.

Pasero, C., (2014). Acute pain. In Nursing diagnosis handbook: An evidence-based guide to planning care

(10th ed., pp. 575-583). Maryland Heights, MO: Mosby Elsevier.

Schepers, MD, N. J., Besselink, MD, PhD, M. B., van Santvoort, MD, PhD, H. C., Bakker, MD, O. J., & Bruno,

MD, PhD, M. J. (2013). Early management of acute pancreatitis. Best Practice & Research Clinical

Gastroenterology, 27, 727-743. Retrieved from PubMed.

Best Practice & Research Clinical Gastroenterology 27 (2013) 727–743

Contents lists available at ScienceDirect

Best Practice & Research Clinical Gastroenterology

8

Early management of acute pancreatitis

Nicolien J. Schepers, MD, PhD Candidate a, d, *,

Marc G.H. Besselink, MD, PhD, Surgeon b,

Hjalmar C. van Santvoort, MD, PhD, Surgical Resident c,

Olaf J. Bakker, MD, PhD Candidate, Surgical Resident c,

Marco J. Bruno, MD, PhD, Professor, Gastroenterologist d,

for the Dutch Pancreatitis Study Group

a Department of Operation Rooms, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

b Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

c Department of Surgery, University Medical Center, Utrecht, The Netherlands

d Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands

Keywords:

Pancreatitis

Pancreas

Diagnosis

Treatment

Review

a b s t r a c t

Acute pancreatitis is the most common gastro-intestinal indication

for acute hospitalization and its incidence continues to rise.

In severe pancreatitis, morbidity and mortality remains high and is

mainly driven by organ failure and infectious complications. Early

management strategies should aim to prevent or treat organ fail-

ure and to reduce infectious complications. This review addresses

the management of acute pancreatitis in the first hours to days

after onset of symptoms, including fluid therapy, nutrition and

endoscopic retrograde cholangiography. This review also discusses

the recently revised Atlanta classification which provides new

uniform terminology, thereby facilitating communication

regarding severity and complications of pancreatitis.

2013 Elsevier Ltd. All rights reserved.

Abbreviations: ACS, abdominal compartment syndrome; CARS, compensatory anti-inflammatory response syndrome; CBD,

common bile duct; CECT, contrast-enhanced computed tomography; ERC, endoscopic retrograde cholangiography; ERCP, endoscopic

retrograde cholangiopancreatography; EUS, endoscopic ultrasound; HES, hydroxyethyl starch; ICU, intensive care unit; IDUS, intra-

ductal ultrasound; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; SIRS, systemic in-

flammatory response syndrome.

* Corresponding author. Dutch Pancreatitis Study Group, HP 690, Radboud University Nijmegen Medical Center, PO Box 9101,

6500HB Nijmegen, The Netherlands. Tel.: þ31 614411960; fax: þ31 243613834.

E-mail address: [email protected] (N.J. Schepers).

1521-6918/$ – see front matter 2013 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.bpg.2013.08.007


http://www.sciencedirect.com/science/journal/15216918

mailto:[email protected]


728 N.J. Schepers et al. / Best Practice & Research Clinical Gastroenterology 27 (2013) 727–743

Introduction

Acute pancreatitis is the most common gastro-intestinal reason for acute hospitalization in the

United States with annually more than 270,000 admissions and estimated costs of 2.6 billion dollars

[1]. The incidence of acute pancreatitis continues to rise and the burden on patients and society is

expected to increase even more [1–3].

Acute pancreatitis is an inflammatory process that is initiated by intra-acinar activation of pro-

teolytic pancreatic enzymes, which ultimately leads to autodigestive injury of the pancreatic gland.

Modulated by cytokines and other inflammatory mediators, intrapancreatic and extrapancreatic

inflammation is generally accompanied by a systemic inflammatory response syndrome (SIRS).

Acute pancreatitis is associated with an overall mortality rate of up to 5% [1,4]. Approximately 15% of

patients with pancreatitis develop pancreatic or extrapancreatic necrosis, which is associated with

hospitalizations that can often last for several months [4]. These patients have a high risk of compli-

cations such as organ failure or infected necrosis with mortality rates of 35% and 20%, respectively [5].

Early management strategies (i.e. arbitrarily defined as within the first five days) in patients with

acute pancreatitis are aimed at preventing or treating complications such as infections, organ failure

and ultimately mortality.

Immediately after clinical presentation a comprehensive clinical work-up is mandatory and

important decisions regarding management, including supportive care, need to be taken (Table 1). This

review addresses the possibilities for management and early invasive interventions which might

ameliorate the disease course and improve outcome in patients with acute pancreatitis.

Methods

A PubMed search was performed using the terms (pancreatitis (MeSH Terms)) AND (pancreatitis

(Title/Abstract)) NOT (chronic (Title/Abstract) OR carcinoma (Title/Abstract) OR autoimmune (Title/

Abstract)). A restriction in the search to articles in English, studies in human adults and a publishing

date between May 2010 and May 2013, resulted in 672 hits. The titles were scanned manually and

articles of interest regarding early management were reviewed. In addition, the evidence based

guideline on the treatment of acute pancreatitis, established during the International Association of

Pancreatology/American Pancreatic Association annual meeting in 2012, was reviewed. Relevant

literature was extracted from the reference lists of the selected articles.

Diagnosis

The diagnosis of acute pancreatitis is made by fulfilling two of the three following criteria: (1)

abdominal pain, (2) an elevated serum lipase or amylase (>3 times the upper limit of normal), (3)

Table 1

Key points early management in acute pancreatitis.

Diagnosis Acute pancreatitis; two out of three:

B Abdominal pain

B Elevated amylase/lipase >3 times upper limit of normal

B Characteristic findings on CT, MRI or ultrasound

Establish aetiology

Monitor and predict severity (limited accuracy)

Imaging Abdominal ultrasound

CT not routinely advised at admission, only after 4–5 days in case of lack of clinical improvement

Fluid therapy Balanced upon clinical response

5–10 mg/kg/h (no specific recommendation for fluid type)

Bile duct

management

Cholangitis: emergency ERC

Predicted mild biliary pancreatitis: no ERC

Predicted severe biliary pancreatitis: no consensus about value ERC

Nutrition Predicted mild pancreatitis: on patients demand, early start

Predicted severe pancreatitis: no consensus on timing of nutrition

N.J. Schepers et al. / Best Practice & Research Clinical Gastroenterology 27 (2013) 727–743 729

characteristic findings of acute pancreatitis on imaging, usually contrast-enhanced computed

tomography (CECT) [6]. In most cases, acute pancreatitis is diagnosed by abdominal pain and an

elevated serum lipase or amylase. In certain circumstances, for instance longer duration of com-

plaints where serum amylase and lipase levels may have normalized, sedated patients or in case of

suspected early complications, additional imaging is required. Characteristic findings of acute

pancreatitis on CECT or magnetic resonance imaging (MRI), confirm the diagnosis [7–9]. As a CECT

early in the disease course may underestimate the extent of pancreatic or extrapancreatic necrosis,

and often does not result in a change in management, it should not be performed routinely at

admission [7,10,11].

Key points diagnosis

➢ Acute pancreatitis, two out of three; (1) abdominal pain, (2) >3 times elevated serum lipase

or amylase (3) characteristic findings of acute pancreatitis on imaging.

➢ CECT is not routinely advised at admission.

Clinical course

The initial phase of acute pancreatitis is characterized by pancreatic inflammation that usually

presents as SIRS [12,13]. Approximately 30% of patients develop SIRS within 48 h after admission

[13]. Persistent organ failure is the key determinant of mortality in acute pancreatitis and is asso-

ciated with a mortality of 25–35% [5,13–15]. In theory, SIRS is followed by a compensatory anti-

inflammatory response syndrome (CARS), a state of immune suppression, making patients more

susceptible for infections including infection of pancreatic necrosis [16]. The mortality in the second

phase of acute pancreatitis is mostly caused by infected necrotizing pancreatitis [15].

About 85% of patients with acute pancreatitis develop interstitial oedematous pancreatitis [4].

The inflammatory oedema of the pancreas usually resolves within one week [17]. Necrosis occurs in the

approximately other 15% of patients, which can involve the pancreatic parenchyma, extrapancreatic

tissues or both [6,18]. Extrapancreatic necrosis alone is associated with fewer complications as

compared to solely parenchymal necrosis. However, once infection of extrapancreatic necrosis occurs,

mortality rate is similar as for infected pancreatic parenchymal necrosis [19]. The recent revision of the

Atlanta classification describes pancreatic and extrapancreatic collections in order to provide a

consistent, worldwide classification in terminology. This description differentiates acute extrap-

ancreatic fluid collection, pancreatic pseudocyst, acute necrotic collection and walled-off necrosis [6].

Table 2 provides definitions, according to the revisited Atlanta, of the morphological features in acute

pancreatitis.

Key points clinical course

➢ Persistent organ failure is defined as >48 h, transient as 48 h.

➢ Persistent organ failure is the key determinant of mortality. ➢ Pancreatic necrosis can involve the pancreatic parenchyma, extrapancreatic tissues or both.

Predicting severity

Prognostic scoring systems have been developed to identify patients with a high risk of severe

pancreatitis for three reasons. First, they may determine which patients need intensive monitoring


Table 2

Definitions in acute pancreatitis [6,116].

Interstitial oedematous pancreatitis Inflammation of pancreatic parenchyma and extrapancreatic tissue,

without necrosis

Necrotizing pancreatitis Parenchymal and/or extrapancreatic necrosis

Severity

Mild No organ failure or local/systemic complications

Moderate Transient organ failure or local/systemic complications

Severe Persistent organ failure (>48 h)

Intra-abdominal hypertension >12 mmHg, technique described in guideline [116]

Abdominal compartment syndrome >20 mmHg and new organ failure

Collections

Acute extrapancreatic fluid

collection

Extrapancreatic fluid associated with interstitial oedematous pancreatitis

Pancreatic pseudocyst Encapsulated collection of fluid without necrosis, after interstitial oedematous

pancreatitis

Acute necrotic collection Collection containing fluid and necrosis associated with necrotizing

pancreatitis

Walled-off necrosis Encapsulated collection in necrotizing pancreatitis

on high dependency units because of a high risk of organ failure. Second, the subgroup of patients

can be selected in whom early, aggressive intervention is indicated. Third, they may be used to

stratify patients in clinical trials with different (predicted) severities of acute pancreatitis [20].

The accuracy of the scoring systems, however, remains disappointing. In clinical practice their

use is further limited by the complexity of many scoring systems. There are several scoring systems

that are based on a combination of clinical and biochemical parameters (Acute Physiology and

Chronic Health Evaluation (APACHE)-II, the Ranson score, Modified Glasgow or Imrie score, C-

reactive protein, Bedside Index of Severity in Acute Pancreatitis (BISAP), Harmless Acute Pancrea-

titis Score (HAPS) and blood urea nitrogen (BUN)). A systematic review demonstrated that most

prognostic variables and scoring systems have high negative predictive values, but low positive

predictive values regarding positive predictive power [21]. In addition, CECT scoring systems can

assess the extent of the morphological abnormalities. As they do not outperform clinical scoring

systems with regard to prognosis, a CECT at admission solely for severity assessment is not rec-

ommended [11]. Recently a head-to-head comparison was performed on the accuracy of the scoring

systems in predicting persistent organ failure [22]. Receiver operating characteristic analysis at

admission showed modest results (0.62–0.84 in the training cohort and 0.57–0.74 in the validation

cohort). Although the modified Glasgow score served as best predictor, the conclusion was drawn

that the presently available scoring systems have reached their maximal performance and that

combining clinical scoring systems does not further improve predictive value. To improve early

management in patients with acute pancreatitis, there still remains a need for accurate markers to

predict the disease course.

Simple laboratory values – such as BUN and creatinin – and more complex laboratory scoring

systems have shown to have similar accuracies [22,23]. In line with their simplicity for clinical use, the

upcoming IAP/APA guidelines recommend persistent SIRS (>48 h) as a marker to predict severity

because of its easy utility and worldwide recognition, while awaiting more accurate scoring systems

[13,24,25]. The fact that persistent organ failure is the key determinant of mortality in pancreatitis

plays an important role in this recommendation.

The revised Atlanta classification has three groups of clinical severity: mild, moderate and severe

pancreatitis. ‘Mild’ pancreatitis is characterized by no organ failure or extrapancreatic collections.

‘Moderate’ pancreatitis, has transient organ failure ( 48 h) or extrapancreatic collections. ‘Severe’

pancreatitis involves persistent organ failure (>48 h). Prospective studies are needed to identify the

validity and clinical use of the classification and the first validation study has recently been published

[26]. Some authors have suggested to divide clinical severity into four groups [27].


Key points predicting severity

➢ None of the available scoring systems for predicting severity is clearly superior, and new

markers are needed.

➢ The revisited Atlanta classification defines mild, moderate and severe pancreatitis.

Aetiology

Although several factors are known to potentially cause acute pancreatitis, the exact pathogenesis

remains unclear [28]. There is a large variation in aetiology of acute pancreatitis between countries.

Most cases of acute pancreatitis are caused by biliary stones or sludge, followed by alcohol abuse

[29,30]. The rise in incidence of acute pancreatitis has been attributed to either the increase of

abdominal obesity – a risk factor for gallstones – ageing or an increase of alcohol consumption [2,30–

32]. Less frequent causes of pancreatitis are hypercalcaemia, hypertriglyceridemia, endoscopic retro-

grade cholangiopancreatography (ERCP), medication and trauma.

The aetiology of pancreatitis should be determined on admission as this tailors management

strategies. Medical history (gallstone disease, alcohol abuse, medication, metabolic syndromes),

physical examination and biochemical tests (liver tests, calcium, triglycerides) help to differentiate

between biliary and metabolic causes [33].

Diagnosing biliary pancreatitis in the early course of the disease may be difficult. The first challenge

is to reliably ascertain whether common bile duct (CBD) stones are present. Unfortunately, clinical

predictors of biliary obstruction (i.e. cholestatic liver enzymes) and radiologic findings have shown to

be unreliable in predicting the presence of CBD stones in the early stages of biliary pancreatitis [34].

Elevations of biochemical markers, such as bilirubin, alkaline phosphatase, gamma-

glutamyltransferase, alanine aminotranferase (ALAT) and aspartate aminotransferase suggest a

biliary cause. However, about 15–20% of the patients with biliary pancreatitis manifest with normal

liver function tests [35]. ALAT is thought to be the most useful biochemical marker in predicting a

biliary origin in acute pancreatitis. An ALAT level of >150 IU/L (2.55 mkat/L, an approximately three-fold

elevation) has been shown to have a positive predictive value of 88–100% in determining a biliary

origin [36–38]. Within 48 h of hospital admission, an ALAT level of >80 IU/L (1.00 mkat/L, an

approximately two-fold elevation) is also associated with a high probability (positive predictive value

79–100%) of biliary pancreatitis [33,39].

Abdominal ultrasound should be performed at admission to detect gallstones or sludge. The choice

for this non-invasive imaging modality is often made because of its availability and low costs.

Abdominal ultrasound has a high sensitivity for cholecystolithiasis, but has a low sensitivity (20%) for

stones in the CBD in acute pancreatitis and can be troublesome in obese patients [34,40]. CECT is also

not attractive as a test for CBD stones as sensitivity is 40% [40]. Finally, of the non-invasive imaging

modalities, the result of a head-to-head comparison study of the ability of magnetic resonance chol-

angiopancreatography (MRCP) to detect choledocholithiasis in biliary pancreatitis was high, approxi-

mately 90% [40,41]. However, small gallstones (<5 mm) in the common bile duct can be easily missed

on MRCP [42]. This is particularly relevant as especially small stones are known to cause biliary

pancreatitis [43].

Of all imaging modalities, endoscopic ultrasound (EUS) is clearly superior in detecting chol-

edocholithiasis, with a high sensitivity and specificity of 89–96% [36,44,45]. However, EUS has

practical limitations because of its limited availability. The sensitivity of endoscopic retrograde

cholangiography (ERC) is 90% [40]. In contrast to EUS, ERC has a 4–7% risk of developing complica-

tions, which can even be higher in patients with pancreatitis [46,47]. Based on these considerations it

is clear that EUS and MRCP could play an important role in selecting patients for ERC. One study

already showed that 71% of ERCs may be avoided using EUS as guidance [45]. Finally, intraductal

ultrasonography (IDUS) has shown to be the best predictor for detecting choledocholithiasis with a

sensitivity of 95% but obviously requires bile duct cannulation [40].


In about 10–15% of the cases the aetiology of pancreatitis remains unclear, although thorough

investigation with IDUS, EUS or MRCP eventually reveals a biliary origin in a significant amount of

presumed ‘idiopathic cases’ [48].

Key points aetiology

➢ Biliary stones or sludge are the most common cause of pancreatitis in most countries.

➢ An ALAT >150 IU/L (>2.55 mkat/L) is highly suggestive for a biliary cause. ➢ EUS or MRCP are modalities of choice to detect CBD stones.

Pain management

The predominant symptom of acute pancreatitis is abdominal pain. In addition to increasing patient

comfort, alleviating pain moderates the physiological response to pain and immunological mecha-

nisms. Intravenous opiates are usually necessary to control pain, though no evidence supports the use

of a specific opiate [4,49]. Oxygen saturation should be monitored, as a side-effect of opiates is res-

piratory suppression.

Fluid therapy

In order to prevent intravascular volume depletion, hypoperfusion and organ failure, adequate fluid

resuscitation is critical in the early management of acute pancreatitis to reduce complications and

mortality [50,51]. In clinical practice, extensive fluid resuscitation is used as this is thought to maintain

the microcirculation of the pancreas [52]. Recently, two randomized trials showed that too aggressive

fluid therapy may result in higher mortality. The first trial compared infusion rates of 10–15 mg/kg/h

with 5–10 mg/kg/h [53]. The second trial compared slow to rapid haemodilution aiming at a turning

point of a haematocrit of 35% within 48 h [54]. Based on the available literature, it can be concluded

that an infusion rate of 5–10 ml/kg/h seems appropriate, balanced upon clinical response (urine output

and heart rate) [25]. Few studies have investigated the type of fluid that should be administered

[55,56]. Recent data suggests that Ringer’s lactate solution is superior to saline solution in preventing a

SIRS [56]. Others suggest that a combination of normal saline, hydroxyethyl starch (HES) and glutamine

is more efficient in resuscitation of severe pancreatitis by reducing SIRS [57]. In contrast, in a multi-

center, blinded, randomized trial, patients with severe sepsis who were resuscitated with HES, had an

increased risk of death and were more likely to require renal-replacement therapy, compared to those

receiving Ringer’s acetate [58]. A recent systematic review concluded that there is a lack of quality

evidence on fluid therapy in acute pancreatitis [59]. In conclusion, fluid resuscitation is a cornerstone in

the treatment of pancreatitis and should be balanced upon clinical response.

Key points fluid therapy and pain management

➢ An infusion rate of 5–10 ml/kg/h with response monitoring is appropriate for most patients.

➢ There is no clear superior type of fluid, more studies are needed.

Bile duct management

Especially small gallstones and sludge are associated with an increased risk of biliary pancreatitis

[43]. The exact pathogenesis of biliary pancreatitis remains unknown [60]. Once biliary obstruction is

thought to be present, decompression is thought to improve the disease course.

Since the introduction of ERC in the seventies as a diagnostic and therapeutic tool, it has become the

standard treatment modality for patients with choledocholithiasis in biliary pancreatitis [61]. In order


to improve the outcome in biliary pancreatitis by decompression of the ampullary orifice and the bile

duct, the effects of ERC have been investigated in experimental and clinical studies [62–65]. These

studies suggest that a temporary biliary obstruction does not only initiate an attack of biliary

pancreatitis, but also aggravates the disease course. Furthermore, post-mortem studies identified

stones in the CBD of patients that died of necrotizing pancreatitis [66,67]. In the view of these findings,

biliary decompression might be a potential life-saving intervention.

On the other hand, ERC plus endoscopic sphincterotomy is an invasive procedure associated with a

complication rate of 8–10% and mortality rate of approximately 1% [68,69]. It is well known that in

many patients CBD stones pass spontaneously in which case an ERC would be redundant [70,71].

In the past decades several randomized trials investigated the role of ERC in biliary pancreatitis.

There is an undisputed indication for an urgent ERC in case of cholangitis [72,73]. Endoscopic biliary

decompression and drainage reduces complications and mortality of patients with cholangitis due to

choledocholithiasis [74]. However, it remains challenging to diagnose cholangitis in a patient with SIRS

due to acute pancreatitis and its definition differs among randomized trials in pancreatitis; from

Charcot’s triad [75] to leaving the decision to an Expertpanel [66], or not reporting the definition of

cholangitis [65,76]. Diagnostic criteria for cholangitis are not based on patients with acute (biliary)

pancreatitis. Initially Charcot’s triad of jaundice, abdominal pain and fever was used, later the Tokyo

Guidelines (TG07) were presented to increase accuracy [77]. Recently the Tokyo Guidelines (TG13)

where updated in which an inflammatory response is defined as a temperature >38 C or a CRP 1 mg/

dL [73]. Randomized trials of ERC in biliary pancreatitis consistently used higher cut-off values

implicating that the diagnosis of cholangitis in the setting of pancreatitis is a separate entity. If the TG13

are applied, it is likely that patients with acute biliary pancreatitis are misclassified with cholangitis

and therefore might undergo a redundant ERC. Future research should focus on the appropriate

diagnostic criteria for cholangitis in the setting of acute biliary pancreatitis.

Persistent biliary obstruction is considered as an indication for ERC [4,49,78,79], although there is

no ‘official’ definition for biliary obstruction. Previously we mentioned the limitations of the

biochemical and imaging modalities in detecting choledocholithiasis in the early setting of acute biliary

pancreatitis [34]. Early ERC may be beneficial in patients with cholestasis. However, this suggestion is

based on randomized trials with varying diagnostic criteria for cholestasis and enrolment of patients

with or without cholestasis. A prospective observational cohort study demonstrated ERC reduced

complications in patients with predicted severe pancreatitis and cholestasis [80].

There is consensus in international guidelines that ERC is not beneficial in predicted mild biliary

pancreatitis [4,49,79].

International guidelines and meta-analyses are conflicting on the subject of ERC in predicted severe

biliary pancreatitis [4,49,79,81]. The UK guidelines state that an urgent ERC is indicated in predicted

severe biliary pancreatitis. The American Gastroenterological Association, the American College of

Gastroenterology and the Italian association state that early ERC in predicted severe biliary pancreatitis

without signs of cholangitis is controversial [4,49,78]. These guidelines are based on different selection,

analysis and interpretation of available studies, which is explained by several limitations in the indi-

vidual study designs [65,66,75,76,82]. First, different scoring systems to predict the severity of the

disease and improper selection criteria were used. This increases the risk for misclassification by

including patients with a predicted mild disease course and with cholangitis. In addition, no criteria

were set to guarantee that the ERC was performed by an experienced endoscopist to avoid a high failure

cannulation and complication rate [76,82]. The criteria for a biliary aetiology were suboptimal, so that for

example in the study of Fan et al only 65% of the patients had true biliary pancreatitis. In the randomized

trials the definition for ‘early’ ERC varied from within 24 h to 72 h after admission or onset of pain. Studies

suggest that the duration of duct obstruction is correlated to the severity of the pancreatitis [62,83].

According to this, ERC should be performed as early as possible. In the studies of Neoptolemos and Fan a

sphincterotomy was only performed in case CBD stones were identified at ERC [66,82]. A meta-analysis

revealed that only 53% of the patients received a sphincterotomy [84], although a prospective obser-

vational study found that sphincterotomy was associated with a reduction of overall complication rate

implying that sphincterotomy should be an integral part of ERC treatment [80].

A recent Cochrane meta-analysis studying the role of early ERC in gallstone pancreatitis, found no

significant improvement in mortality, and local and systemic, complications, regardless of the


predicted severity [72]. Besides the limitations in study design of the included trials, the pooled sample

size of patients with predicted severe biliary pancreatitis is small and thus statistically underpowered

to draw definite conclusions.

The potential beneficial effect of ERC in the subgroups of predicted severe biliary pancreatitis,

should be evaluated in future research with a sufficient number of patients, and statistical power, to

detect differences in outcome. A randomized controlled trial in patients with predicted severe biliary

pancreatitis without cholangitis is currently ongoing (ISRCTN97372133).

Key points bile duct management

➢ Urgent ERC is indicated in case of cholangitis.

➢ ERC is not indicated in predicted mild pancreatitis, regardless of persistent cholestasis. ➢ ERC is possibly indicated in patients with cholestasis. ➢ ERC is possibly indicated in patients with predicted severe pancreatitis.

Prevention of infection

Infection prophylaxis would seem a useful strategy since infectious complications have a significant

impact on mortality [85]. Bacteraemia in acute pancreatitis is an independent predictor for mortality

and increases the risk of infected necrosis [85].

For decades the prophylactic role of antibiotics has been subject of discussion. Randomized trials on

antibiotic prophylaxis in acute pancreatitis showed conflicting results [86–89]. This is most likely

caused by limitations in the study design, such as different inclusion criteria and the type of antibiotics

that were used. Based on the most recent meta-analyses, guidelines advise that antibiotics should not

be prescribed routinely as prophylaxis [90,91].

Selective decontamination of the intestinal tract reduces mortality in general (non-pancreatitis)

intensive care unit (ICU) patients [92]. In line with these results, beneficial effects of selective

decontamination in severe acute pancreatitis have been observed [93]. Although in this study, selective

decontamination reduced infection of pancreatic necrosis, the study design has been criticized. The

study was not placebo-controlled, nor was it blinded and no statistically significant reduction in

mortality was observed. In addition, the beneficial effect might be due to the simultaneous adminis-

tration of intravenous antibiotics for (suspected) non-pancreatic infections such as pneumonia.

Furthermore, the potentially beneficial results should be weighed against an increase in antibiotic

resistance, gram-positive overgrowth or fungi colonization [94].

Probiotic prophylaxis was hypothesized to reduce infectious complications in acute pancreatitis.

A large randomized-placebo controlled trial (PROPATRIA) in patients with predicted severe

pancreatitis found no effect on infectious complications but an increased rate of bowel ischaemia

and mortality in patients who received probiotics [95]. Therefore, use of probiotics (at least the

mixture of probiotics used in the PROPATRIA study) is strongly discouraged in patients with pre-

dicted severe pancreatitis, although the exact pathophysiological mechanism of this adverse effect

remains unknown [96].

Many prophylactic strategies focus on reducing bacterial translocation in relation to the intestinal

permeability [97]. Several studies have been performed to study the role of early nutrition in this

respect.

Key points prevention of infection

➢ Intravenous antibiotics should not be used as prophylaxis.

➢ Enteral probiotics should not be prescribed in patient with pancreatitis.


Nutrition

Nutrition in acute pancreatitis has evolved greatly over the past decades. Initially, it was thought

that feeding would stimulate pancreatic enzyme secretion and that enteral nutrition should be avoi-

ded. Over time, the key role of maintaining the integrity of the intestine became evident. Feeding

became a supportive measure by which the intestinal mucosal integrity could be preserved and bac-

terial translocation is thought to be reduced [98,99].

Enteral nutrition has proven to be superior to parenteral nutrition regarding the occurrence of

systemic infections, multi-organ failure and mortality [100]. Only in case enteral feeding is not toler-

ated, parenteral nutrition should be initiated to preserve adequate intake [101].

Patients with predicted mild pancreatitis can restart oral feeding on their own request. Immediate

feeding has shown to be safe and leads to shorter hospital stay in patients with predicted mild

pancreatitis [102]. Restrictions with regard to food consistency are not needed, i.e. a full solid diet

resulted in shorter hospital stay in patients with mild pancreatitis [103].

Patients with predicted severe pancreatitis should receive nasoenteral tube feeding only if they

cannot tolerate oral intake. In order to preserve the intestinal function and prevent bacterial trans-

location, it is recommended to initiate enteral nutrition early in the disease course [4,101]. A systematic

review demonstrated that the beneficial effect of nutritional support might be associated with timing

of the start of nutrition [104]. In line, a retrospective analysis of 197 cases demonstrated that early

enteral nutrition (<48 h) was superior to delayed enteral nutrition (>48 h) for the prevention of

infected necrosis and mortality in predicted severe acute pancreatitis [105]. A meta-analysis of early

enteral feeding (<36 h of admission or within 36 h of surgery) in critically care patients showed a

reduction in infectious complications and hospital stay [106]. A randomized trial in 60 patients with

severe acute pancreatitis demonstrated that enteral nutrition within 48 h after admission can mod-

erate the immune response and improve outcome compared to start of enteral nutrition after seven

days [107]. A multicenter randomized trial investigating the timing of enteral nutrition in patients with

predicted severe pancreatitis has recently been completed and awaits final analysis (ISRCTN18170985).

Key points nutrition

➢ In predicted mild pancreatitis oral intake can immediately be restarted after admission

without restrictions.

➢ In predicted severe pancreatitis it is unclear whether early enteral nutrition improves outcome.

Recurrent biliary events

After biliary pancreatitis, cholecystectomy or endoscopic sphincterotomy should be performed in

order to prevent recurrent biliary pancreatitis, biliary colics and cholecystitis [4,79]. Endoscopic

sphincterotomy has shown to reduce the risk of recurrent biliary pancreatitis, but not of other biliary

events, such as cholecystitis or biliary colics [108]. Therefore, one should strive to always perform a

cholecystectomy early following an attack of biliary pancreatitis unless this is not safe or feasible, e.g. in

older or unfit candidates or in patients with extrapancreatic collections. In these cases endoscopic

sphincterotomy is acceptable [109]. Although sphincterotomy clearly will not prevent recurrent biliary

colics it will virtually eliminate the risk of recurrent biliary pancreatitis [108,110].

The timing of cholecystectomy after mild biliary pancreatitis still is subject to debate. As recurrent

events occur particularly in the first months after recovery from pancreatitis, one should aim for quick

definitive management, provided that cholecystectomy can be performed safely [108,110]. Delay of

cholecystectomy increases the risk of a recurrent biliary event. A randomized trial investigating the

timing of cholecystectomy was prematurely stopped because a beneficial effect in favour of chole-

cystectomy within 48 h after admission was observed [111]. These results should be interpreted with

some caution as the study was not adequately powered to study safety. A recent systematic review


found a readmission rate prior to cholecystectomy in 95 of 515 patients (18%) because of recurrent

biliary pancreatitis, acute cholecystitis, and biliary colics after mild biliary pancreatitis. This study

further showed that early cholecystectomy is probably safe after mild biliary pancreatitis although

selection bias could not be fully excluded [110]. Currently a randomized trial is investigating the effi-

cacy and safety of index cholecystectomy after biliary pancreatitis (ISRCTN72764151) [112].

In severe pancreatitis, with local and systemic complications, cholecystectomy is delayed until

resolution of symptoms or when extraperancreatic collections are resolved, which is usually after six

weeks [79,113]. Little is known about the recurrent events after severe pancreatitis prior to chole-

cystectomy and of the role of endoscopic sphincterotomy. In two retrospective studies no recurrent

events were reported [113,114].

Key points recurrent biliary events

➢ Cholecystectomy should be performed after biliary pancreatitis to reduce the risk of

recurrent biliary events.

➢ In mild pancreatitis current evidence is that cholecystectomy should be performed as soon as possible after recovery. A randomized trial is needed.

➢ In severe pancreatitis cholecystectomy should be delayed until resolution of symptoms or when extraperancreatic collections are resolved.

Intensive care

The intensity of clinical monitoring in acute pancreatitis is best based on the presumed risk of

deterioration and therefore the predicted severity of acute pancreatitis. Clinical parameters,

described by the Society of Critical Care Medicine, can be used to triage for ICU admission [115]. The

crux in the management with acute pancreatitis is adequate fluid resuscitation (see section fluid

therapy) and to be aware of the occurrence of early complications that require intervention. Rapid

deterioration might be due to an abdominal compartment syndrome (ACS). A 2013 international

conference of experts defined ACS as an intra-adominal pressure of >20 mmHg and new organ

failure [116]. Sometimes a period of intra-abdominal hypertension (IAH), defined as 12 mmHg, is

observed prior to the new onset of organ failure. ACS and IAH have shown to contribute in gut

barrier failure [117]. Reported incidence rates of IAH are high between 59 and 78% in acute

pancreatitis and a portion of 27% developed ACS [118,119]. An extremely high mortality rate of ACS

up to 83% has been described [120].

The initial step in the treatment of ACS is to immediately lower abdominal pressure using naso-

gastric decompression, laxantia and muscle relaxants [116]. If clinical improvement is not achieved,

percutaneous drainage of intra-peritoneal fluid should be attempted. If this does not suffice, surgical

decompressive laparotomy is probably indicated. Animal studies suggest that there is a narrow time

window for surgical intervention [121–123]. A randomized trial comparing decompressive laparotomy

with percutaneus puncture with placement of abdominal catheter in patients with severe pancreatitis

and ACS, is currently ongoing (NCT00793715) [124].

Key point intensive care

➢ Abdominal compartment syndrome is associated with high mortality and requires prompt

intervention.

➢ Optimal treatment of abdominal compartment syndrome is currently unclear. ➢ There is a 2013 international consensus guideline on the management of abdominal

compartment syndrome [116].


Fig. 1. Flow-chart early management of acute pancreatitis.

Necrotizing pancreatitis

Sterile necrosis can be treated without invasive intervention in the vast majority of patients [18].

Around 30% of patients will develop infected necrosis [5,6]. Infected necrosis increases the death rate to

approximately 30% [15,18]. Infection is considered proven if gas is present in the extrapancreatic

collection or when fine-needle aspiration is positive for bacteria or fungi on gram stain and culture

[6,125]. There is no need for routine fine-needle aspiration in patients with clear clinical or imaging signs

of infected necrotizing pancreatitis as there is a small (10–25%) risk of false negative results [126,127]. It is

generally accepted to administer intravenous antibiotics in case of suspected infected necrosis to mitigate

additional infectious complications [128]. Intervention to drain infected fluid or remove infected necrosis

is justified in patients with progressive clinical deterioration despite maximal supportive therapy [18].

Currently it is common practice that intervention should be delayed until approximately four weeks in

order to minimize the risks of complications during intervention, in particular necrosectomy [18].

Infected necrosis should be treated by a step-up approach [18,129], consisting of catheter drainage,

either percutaneously or endoscopic transluminal, if necessary followed by surgical or endoscopic


necrosectomy. A pilot randomized trial found endoscopic transgastric necrosectomy to be superior to

surgical necrosectomy in terms of new organ failure and overall complications [130]. An adequately

powered randomized trial, comparing the surgical step-up approach versus the endoscopic step-up

approach in patients with infected pancreatic necrosis, is currently ongoing (ISRCTN09186711).

Key points necrotizing pancreatitis

➢ Infected necrosis is nearly always an indication for intervention.

➢ Interventions should ideally be postponed until the collection has become walled-off (typically >4 weeks) as this reduces complications.

➢ Infected necrosis should be treated by a step-up approach, which starts with catheter drainage, if needed followed by (minimally invasive) necrosectomy.

Summary

Acute pancreatitis is a common disease with a rising incidence. Recently, the revised Atlanta

classification presented new definitions on clinical severity and new terminology for extrapancreatic

collections (Table 1). Diagnosing acute pancreatitis also involves predicting the severity and estab-

lishing the aetiology to tailor management strategies in the early phase of acute pancreatitis. Recent

guidelines recommend SIRS as marker to predict severity because of its ease of use and its ability to

perform as good as complex models. An elevated ALAT (>150 IU/L) indicates a high probability of a

biliary origin. MRCP or EUS should be performed to detect the presence or absence of CBD stones.

Early management strategies in pancreatitis are based on preventing or treating organ failure and

preventing infectious complications (Fig. 1). Fluid resuscitation at an infusion rate of 5–10 ml/kg/h is

regarded as a cornerstone in the treatment of pancreatitis, although high quality studies supporting its

use are eagerly awaited. The approach to nutrition and feeding in acute pancreatitis has radically

changed over time. A pro-active approach with early enteral feeding is advocated in order to maintain

gut integrity. In mild pancreatitis oral intake can usually be resumed quickly after hospital admission.

In severe pancreatitis it is unclear whether early enteral nutrition improves outcome. Antibiotics

should not be administered prophylactic. In case of biliary pancreatitis, urgent ERC should be per-

formed only in case of cholangitis and possibly in patients with cholestasis. ERC is not indicated in

predicted mild pancreatitis. In predicted severe biliary pancreatitis, the role of early ERC still needs to

be determined. Cholecystectomy should be performed early to reduce readmissions for biliary events.

In cases with severe pancreatitis it is appropriate to delay cholecystectomy to six weeks after the onset

of acute pancreatitis. In patients with severe acute pancreatitis, rapid deterioration may be due to

abdominal compartment syndrome or infected pancreatic necrosis which are conditions that are

associated with a high mortality rate and require intervention.

Practice points

Acute pancreatitis is the most common gastro-intestinal reason for acute hospitalization and

the incidence is rising.

An elevated ALAT >150 IU/L (2.55 mkat/L) is a good predictor for a biliary origin.

Initial treatment should consist of:

B Effective pain control

B Infusion rate 5–10 ml/kg/h, adjusted upon clinical response

B Imaging: abdominal ultrasound at admission. EUS or MRCP to detect CBD stones.

ERC does not improve outcome in predicted mild biliary pancreatitis.

Urgent ERC with sphincterotomy is indicated in case of cholangitis.

Extrapancreatic fluid collections are classified as acute extrapancreatic fluid collection,

pancreatic pseudocyst, acute necrotic collection and walled-off necrosis.


Research agenda

Accurate markers to predict severity of the disease course.

Validation of the proposed classifications for severity of pancreatitis.

Fluid therapy in acute pancreatitis.

Diagnostic criteria for cholangitis in the setting of acute biliary pancreatitis.

Role of early ERC in predicted severe biliary pancreatitis.

Timing of enteral nutrition in predicted severe pancreatitis.

Timing of initial intervention in infected necrotizing pancreatitis.

Funding

N.J. Schepers is sponsored by The Netherlands Organization for Health Research and Development

(ZonMw, grant number 837002008) and the Foundation for Health Care Subsidies (Fonds NutsOhra,

grant number 1203-052) to perform clinical studies on acute pancreatitis. The sponsor had no

involvement in any stage of the manuscript.

Conflict of interest

None.

Acknowledgements

N.J. Schepers drafted the manuscript. All authors edited the manuscript. All authors approved the

final manuscript.

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Original article

Altered central pain processing after pancreatic surgery for

chronic pancreatitis S. A. Bouwense1 , U. Ahmed Ali3 , R. P. ten Broek1 , Y. Issa4 , C. H. van Eijck5 , O. H. Wilder-Smith2

and H. van Goor1

Departments of 1 Surgery and 2 Anaesthesiology, Pain and Palliative Care, Radboud University Nijmegen Medical Centre, Nijmegen, and Departments of

Surgery, 3 University Medical Centre Utrecht, Utrecht, 4 Academic Medical Centre, Amsterdam, and 5 Erasmus Medical Centre Rotterdam, Rotterdam,

The Netherlands

Correspondence to: Professor H. van Goor, Department of Surgery, Radboud University Nijmegen Medical Centre, PO Box 9101/690, NL-6500 HB

Nijmegen, The Netherlands (e-mail: [email protected])

Background: Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered

central pain processing. This study evaluated the relationship between pain processing and pain outcome

after pancreatic duct decompression and/or pancreatic resection in patients with CP.

Methods: Patients with CP underwent quantitative sensory testing. Pain processing was measured via

electrical pain detection (ePDT) and electrical pain tolerance (ePTT) thresholds in dermatomes C5 and

L4. Inhibitory descending pain control mechanisms were assessed using the conditioned pain modulation

(CPM) paradigm. Healthy controls and patients with CP were compared, and patients with CP and a

poor pain outcome (visual analogue scale (VAS) score greater than 30) were compared with those with a

good pain outcome (VAS score 30 or less).

Results: Forty-eight patients with CP had lower ePDT, ePTT and CPM responses compared with

values in 15 healthy controls (P < 0·030). The sum of ePDT values was lower in patients with a poor

pain outcome than in those with a good outcome (median 7·1 versus 11·2 mA; P = 0·008). There was a

correlation with the VAS score and the sum of ePDT values (rS = −0·45, P = 0·016) and ePTT values

(rS = −0·46, P = 0·011), and CPM response (rS = −0·43, P = 0·006) in patients with CP.

Conclusion: After pain-relieving pancreatic surgery, patients with CP exhibit altered central pain

processing compared with that in healthy controls. Poor pain outcomes are associated with more central

sensitization and more pronociceptive descending pain modulation, and this should be considered when

managing persistent pain after pain-relieving surgery for CP.

Presented in part to the 7th Alpine Liver and Pancreatic Surgery Meeting, Madonna di Campiglio, Italy,

January 2012, and the American Pancreatic Association/International Association of Pancreatology Joint Annual

Meeting, Miami, Florida, USA, October – November 2012; published in abstract form as Pancreas 2012; 41: 1350

Paper accepted 9 September 2013

Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9322

Introduction

Pain control in chronic pancreatitis (CP) can be a

challenge1,2 . As pain progresses during the course of CP,

a substantial group of patients have multiple endoscopic

and/or surgical interventions in an attempt to alleviate

the pain3 – 7 . Even when these invasive procedures are

technically successful, some patients continue to suffer

pain. This group of patients tends to be refractory to further

classical pain management, exhibiting opioid dependence,

failure of nerve blockade, recurrent hospitalization and

impaired quality of life1,8,9 .

A possible explanation for this type of intense chronic

pain involves changes in the central nervous system (CNS)

due to chronic nociceptive input10 . Ongoing nociceptive

input, caused by nerve damage and local inflammation, is

increasingly recognized to result in altered pain processing

at spinal and supraspinal levels of the CNS11,12 . Together

with the loss of descending inhibitory control mechanisms

and activation of descending facilitation, this central

sensitization is manifest as generalized hyperalgesia13 .

Ultimately, these changes may become independent of

nociceptive input, thus maintaining the chronic pain

state14 .

2013 British Journal of Surgery Society Ltd British Journal of Surgery 2013; 100: 1797 – 1804

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1798 S. A. Bouwense, U. Ahmed Ali, R. P. ten Broek, Y. Issa, C. H. van Eijck, O. H. Wilder-Smith and H. van Goor

Accumulating evidence9,10,15,16 supports this view of

chronic pain in CP. Insight into various aspects of

pain processing in patients with CP has been gained

using experimental pain models and explored by quan-

titative sensory testing (QST), electroencephalography or

functional magnetic resonance imaging (fMRI)9,10,17 – 19 .

These approaches are further supported by recent findings

demonstrating that treatment with S-ketamine infusion,

pregabalin and thoracoscopic splanchnicectomy is accom-

panied by a reduction in generalized hyperalgesia15,16,20 .

Based on the hypothesis that poor clinical pain outcomes

after pancreatic surgery are associated with more central

sensitization and less effective inhibitory modulation, the

aim of this study was to explore the relationship between

pain outcomes based on pain experience and altered central

pain processing in patients with CP who had undergone

pancreatic surgery for pain relief, in the hope of being

able to target and design more effective therapies for this

group.

Methods

Consecutive patients with CP who underwent pancreatic

surgery for pain were identified from electronic registries

for surgical procedures at three Dutch university hospitals

(Radboud University Nijmegen Medical Centre, Univer-

sity Medical Centre Utrecht and Erasmus Medical Centre

Rotterdam) with special interest in the treatment of CP.

The period of inclusion varied from 8 to 15 years between

centres. Inclusion criteria were confirmed diagnosis of CP

and that the primary indication for surgery was pain. All

patients were aged 18 years or more.

Patients included in the study underwent either

a drainage procedure (pancreaticojejunostomy), a

duodenum-preserving pancreatic head resection (Beger

or Frey procedure), a pancreaticoduodenectomy or a

left-sided pancreatic resection (tail resection)21 – 23 . The

indication for the type of surgery was based on the location

of pathological changes in the pancreas on preoperative

computed tomography or MRI. All procedures were

considered a technical success by the operating surgeon.

Patients with other indications for pancreatic surgery,

previous pancreatic surgery and known malignancy at

time of operation were excluded. None of the patients

had a new endoscopic or surgical intervention after the

pancreatic drainage or resection procedure.

For inclusion in the study, patients needed to have a

history of chronic abdominal pain typical of pancreatitis

(dull epigastric pain more than 3 days per week for at least

3 months) and a diagnosis of CP based on Mayo Clinic

diagnostic criteria5 .

The local institutional review board waived the need for

formal ethics committee approval because the study was

purely observational, and because the QST measurements

were performed routinely in patients with chronic pain

in these institutions. Subjects gave informed consent to

participate. The study was conducted according to the

guidelines of the Central Committee on Research involving

Human Subjects in the Netherlands and the principles

outlined in the Declaration of Helsinki24 .

A healthy control group recruited for an earlier trial was

used to confirm the presence of spreading hyperalgesia

in the CP group20 . Control subjects had no history of

a medical condition that could alter pain processing or

interfere with pain measurements. Clinical data

Pain was assessed using a 0 – 100 visual analogue scale

(VAS), with a score of zero being no pain and 100 the

worst imaginable pain25 . Patients with CP were allocated

to either a poor (score above 30) or good (score 30 or

less) pain outcome group based on their postoperative

VAS score. The Izbicki pain score26 was measured

during outpatient visits. Baseline characteristics consisted

of age, sex, duration of pain symptoms before surgery,

preoperative and postoperative use of opioid analgesics,

type of surgical procedure, time from operation until

measurement and continued alcohol or tobacco use27 – 29 . Quantitative sensory testing

QST was performed by technicians who were blinded for

group allocation, using a standard temporal test sequence10 .

Testing in women was not standardized with regard to

phase of the menstrual cycle because all of the female

patients were amenorrhoeic. All patients were asked to

fast before testing. After initial QST training, electrical

pain detection (ePDT) and electrical pain tolerance

(ePTT) thresholds to constant-current electrical skin

stimulation (Digistim; Biometer, Copenhagen, Denmark),

tetanic stimulation at 100 Hz, 0·2-ms square waves, self-

adhesive electrodes 3 cm apart, were obtained at each of

the following sites on the dominant body side: lower neck

(C5 dermatome) and knee (L4 dermatome), on the basis

that both dermatomes are distant from the pancreatic

dermatome and were chosen to observe spreading (or

generalized) hyperalgesia15 .

The conditioned pain modulation (CPM; previously

known as diffuse noxious inhibitory control) paradigm was

performed to test the ability of the patient to generate

descending inhibitory modulation30,31 . The ePTT (test

2013 British Journal of Surgery Society Ltd www.bjs.co.uk British Journal of Surgery 2013; 100: 1797 – 1804



Central pain processing after surgery for chronic pancreatitis 1799

stimulus) was determined before and after the cold pressor

task (conditioning stimulus), and the CPM effect was

determined as the relative (percentage) change in ePTT. A

negative CPM response implies pronociceptive descending

pain modulation. For the cold pressor task, the dominant

hand was immersed in ice-chilled water (1·0 ± 0·3 ◦ C). The

patient was told to remove their hand from the water after

2 min of immersion, or sooner if the pain was considered

to be intolerable, and the immersion time was noted.

Immediately after the cold pressor task, subjects rated the

pain experienced during the test by use of a VAS for

quality control purposes. The ePTT in the non-dominant

L4 dermatome (knee) was obtained immediately before

and after ice-water immersion. Outcome measures

The primary effect parameter for the study was the

difference in the sum of electrical pain threshold values

for all dermatomes between the two pain outcome groups

and the healthy controls15 . Secondary endpoints were

the differences in pain thresholds for the individual

dermatomes and in CPM response between the pain

outcome groups and healthy controls. Statistical analysis

Statistical analysis was performed using the software

package STATISTICA for Windows , release 7·0

(StatSoft, Tulsa, Oklahoma, USA). Non-normally dis-

tributed data are presented as median (i.q.r.). The

sum of ePDT and ePTT for all dermatomes, and the

CPM results were compared between healthy controls

and all patients with CP using the Mann – Whitney

U test, to confirm spreading hyperalgesia in patients

with CP.

For the CP group as a whole, correlations between

VAS pain score and the sum of thresholds and individual

dermatomal thresholds were determined by Spearman’s

correlation coefficient. Statistical significance was set at

P ≤ 0·050. Subsequent comparisons between good and

poor pain outcome groups, and healthy controls for (sum

of) thresholds, change in (sum of) thresholds and CPM

were conducted with the Mann – Whitney U test with

the Bonferroni correction for multiple comparisons (good

versus poor outcome, healthy controls versus good outcome,

and healthy controls versus poor outcome). Statistical

significance was set at P ≤ 0·020.

The Mann – Whitney U test was used to analyse

differences in QST pain thresholds between opioid and

nonopioid users. The Kruskal – Wallis test was used for

analysis of differences in QST pain thresholds for opioid

and nonopioid users within the good and poor pain

outcome groups (four groups). A similar analysis was

performed for three other subgroups: cigarette smokers and

non-smokers, alcohol and non-alcohol users, and patients

with and without glucose levels above 10 mmol/l (180

mg/dl).

Results

Enrolment and baseline characteristics

From September 2008 to March 2011, a total of 76 patients

with CP were screened and 48 recruited from a Dutch

study describing clinical outcome in relation to timing

of surgery in chronic pancreatitis32 . Patients declined to

participate for a variety of reasons: travelling distance, no

personal benefit and active relapse of CP. All recruited

patients (13 women and 35 men of median age 49 (i.q.r.

42 – 57) years completed the measurements according to

the protocol and were analysed. The median pain VAS

score at time of examination was 43 (12 – 68) and the

median Izbicki pain score was 56 (25 – 70). Twenty-three

patients (48 per cent) used opioids, with a median opioid

consumption of 45 (11 – 90) mg morphine equivalents/day.

The median time from operation to QST measurement

was 66 (44 – 115) months. Thirty-seven patients (77 per

cent) had a glucose level below 10 mmol/l immediately

before testing. The healthy control group consisted of

15 volunteers (7 women and 8 men of median age

38 (35 – 49) years). Healthy controls were younger than

patients with CP (P < 0·001).

Patients with chronic pancreatitis versus healthy

controls

Electrical pain thresholds

The sum of threshold values for ePDT and ePTT was

significantly lower in the CP group than in healthy controls

(P = 0·024 and P = 0·001 respectively).

Individual ePDT values in dermatome L4 and ePTT

values in dermatome L4 were all significantly lower for

patients with CP than for healthy controls (P = 0·007

and P < 0·001 respectively). Individual ePDT values in

dermatome C5 were significantly lower in the CP group

than in the control group (P = 0·030). Only individual

ePTT values for dermatome C5 were not significantly

lower between the groups (P = 0·177).

Taken together, these results indicate that, compared

with healthy controls, patients with CP exhibit generalized

hyperalgesia to electrical stimulation (Table 1).





Chronic

pancreatitis

PDT (mA)

Healthy

controls

P*

Good pain

outcome

(n = 18)

Poor pain

outcome

(n = 30)

Sum of dermatomes 8·2 (5·1–11·4) 11·2 (8·8–17·7) 0·024 Age (years)* 53 (41 – 58) 48 (42 – 54)

Dermatome C5

Dermatome L4

PTT (mA)

3·7 (2·9–5·6)

4·6 (2·8–5·9)

4·9 (3·4–7·2)

6·3 (4·7–11·1)

0·030

0·007 Sex ratio (M : F)

Aetiology

Alcohol

14 : 4

9 (50)

21 : 9

18 (60)

Sum of dermatomes 11·7 (9·4–15·3) 21·6 (13·7–27·9) 0·001 Biliary 3 (17) 6 (20)

Dermatome C5

Dermatome L4

PM

5·6 (4·6–8·0)

6·1 (4·3–7·2)

8·2 (5·6–12·1)

12·1 (8·1–15·9)

0·177

< 0·001 Other

Surgery

Pancreaticojejunostomy

6 (34)

1 (6)

6 (20)

3 (10)

Latency (s) 72 (26 – 180) 180 (180 – 180) < 0·001 Tail resection 4 (22) 6 (20)

Response (%) −2·7 (−22·1 to 30·1) 32·6 (10·4–41·8) 0·004 Frey procedure 6 (33) 4 (13)

Beger procedure 6 (33) 10 (33) alues are median (i.q.r.). ePDT, electrical pain detection threshold;

Pancreaticoduodenectomy 1 (6) 7 (23)

Table 1 Baseline quantitative sensory testing values in all patients

with chronic pancreatitis versus healthy controls

Table 2 Characteristics of patients with chronic pancreatitis with

good versus poor pain outcome

C

V

ePTT, electrical pain tolerance threshold; CPM, conditioned pain

modulation. *Mann – Whitney U test.

Body mass index (kg/m2 )*

Preop. 20·6 (18·9–22·8) 21·3 (18·8–23·3)

Postop. 22·8 (20·8–24·1) 22·5 (19·5–26·8)

At baseline, patients with CP tolerated the cold pressor

task for shorter periods than healthy controls (P < 0·001).

Subjects in the healthy control group exhibited a

significantly greater CPM response than patients with

CP (P = 0·004) (Table 1). These results indicate that

patients with CP have less effective descending inhibitory

modulation than healthy controls.

Correlations

For the CP group as a whole, a significant negative

sum of ePDT values (rS = −0·45, P = 0·016) and the sum

of ePTT values (rS = −0·46, P = 0·011).

There were also significant negative correlations with

ePDTs for L4 (rS = −0·48, P = 0·009) and ePTTs for C5

(rS = −0·50, P = 0·004), and a negative correlation between

the VAS score and CPM response (rS = −0·43, P = 0·006).

Good versus poor pain outcome group

Eighteen patients with CP and a postoperative VAS score

of 30 or less were allocated to the good pain outcome

group. The other 30 patients had a VAS score above 30 and

were allocated to the poor pain outcome group. The two

groups were comparable for baseline characteristics, except

for the incidence of postoperative endocrine insufficiency,

which was significantly higher in patients with a poor

pain outcome. VAS and Izbicki pain scores were also

significantly higher in the poor pain outcome compared

with the good pain outcome group (Table 2).


The sum of ePDT values for all dermatomes was

significantly lower in the poor pain outcome group than

(days)*

Relapse after surgery (weeks)

> 15 1 (6) 1 (3)

8 – 15 1 (6) 2 (7)

< 8 0 (0) 0 (0)

Postop. alcohol use 9 (50) 10 (33)

Postop. smoking 14 (78) 17 (57)

Opioid use

Preop. 9 (50) 22 (73)

Postop. 7 (39) 16 (53)

Postop. endocrine insufficiency 9 (50) 22 (73)†

Postop. exocrine insufficiency 13 (72) 23 (77)

New-onset diabetes mellitus 6 (33) 15 (50)

Postop. VAS score* 8 (0 – 16) 65 (49 – 74)‡

Postop. time to QST* 88 (55 – 109) 59 (40 – 121)

Values in parentheses are percentages unless indicated otherwise; *values

are median (i.q.r.). VAS, visual analogue scale; QST, quantitative sensory

testing. †P = 0·038, ‡P < 0·001 (Mann – Whitney U test).

in the good pain outcome group (P = 0·008). The sum

of ePTT values was also lower in patients with poor

pain outcomes, although the difference was not significant

(P = 0·051).

For individual dermatomes, electrical pain detection and

tolerance thresholds were significantly lower (ePDT L4:

P = 0·003), or lower without reaching significance (ePDT

C5: P = 0·039; ePTT C5: P = 0·028; ePTT L4: P = 0·079),

for poor pain outcome versus good pain outcome (Table 3).

Based on these results, patients with poor pain outcome

are hyperalgesic compared with those with a good pain

outcome for some measurements.

Conditioned pain modulation response

Clear differences were seen in the cold pressor task

latency and CPM response, but these results did not reach

statistical significance (Table 3).





Table 3 Comparison of baseline quantitative sensory testing results in patients with chronic pancreatitis with good and poor pain

outcome, and in healthy controls

Good pain outcome Poor pain outcome P* Healthy controls P† P‡

ePDT (mA) Sum of dermatomes 11·2 (10·0–12·3) 7·1 (4·7–9·5) 0·008 11·2 (8·8–17·7) 0·726 0·004

Dermatome C5 5·2 (3·9–6·4) 3·4 (2·6–4·7) 0·039 4·9 (3·4–7·2) 0·953 0·06

Dermatome L4

ePTT (mA) 5·9 (4·7–7·3) 3·2 (2·3–5·1) 0·003 6·3 (4·7–11·1) 0·482 0·001

Sum of dermatomes 13·1 (11·5–18·0) 11·3 (6·9–14·5) 0·051 21·6 (13·7–27·9) 0·019 0·001

Dermatome C5 6·9 (5·3–8·6) 4·8 (4·2–7·4) 0·028 8·2 (5·6–12·1) 0·274 0·014

Dermatome L4

CPM 6·5 (5·7–8·0) 4·6 (3·4–6·6) 0·079 12·1 (8·1–15·9) 0·003 <0·001

Latency (s) 113 (42 – 180) 40 (25 – 180) 0·316 180 (180 – 180) 0·001 <0·001

Response (%) 21·3 (−5·8 to 37·1) −12·1 (−40·1 to 21·1) 0·021 32·6 (10·4–41·8) 0·167 0·001

Values are median (i.q.r.). ePDT, electrical pain detection threshold; ePTT, electrical pain tolerance threshold; CPM, conditioned pain modulation.

*Good versus poor pain outcome; †healthy controls versus good pain outcome; ‡healthy controls versus poor pain outcome (Mann – Whitney U test with

Bonferroni correction for multiple comparisons; P ≤ 0·020 was considered statistically significant).

Good pain outcome group versus healthy controls


No difference in the sum of ePDT values was observed

between patients with a good pain outcome and healthy

controls. The sum of ePTT values was significantly lower

in the good pain outcome group (P = 0·019), but individual

dermatomal ePTTs were significantly lower only for

dermatome L4 (P = 0·003).


Patients with a good pain outcome tolerated the cold

pressor task for a much shorter time than healthy controls

(P = 0·001), although the CPM response was comparable

between these two groups (Table 3).

Poor pain outcome group versus healthy controls


The sum of ePDT and the sum of ePTT values were

significantly decreased in patients with a poor pain outcome

compared with healthy controls (P = 0·004 and P = 0·001

respectively).

ePDTs in dermatome L4, and ePTTs in dermatomes

C5 and L4 were all significantly lower in the poor pain

outcome group compared with values in healthy controls

(P = 0·001, P = 0·014 and P < 0·001 respectively).


The length of time for which patients with a poor pain

outcome tolerated the cold pressor task was much shorter

than that for healthy controls (P < 0·001). CPM response

was decreased in patients with a poor pain outcome

(P = 0·001) (Table 3).

Subgroup analysis

No significant differences for electrical pain thresholds

(individual and sum of threshold values) or CPM response

were observed for the subgroups of opioid and non-opioid

users, and within the good and poor pain outcome groups.

Neither were there any significant differences between

cigarette smokers and non-smokers, alcohol and non-

alcohol users, and patients with and without glucose levels

above 10 mmol/l for electrical pain thresholds and CPM

response. Testing for these three variables within the good

and poor pain outcome groups revealed no differences in

QST pain thresholds.

Discussion

Patients with CP who had a good pain outcome (low

VAS score) after pancreatic surgery still exhibited some

signs of hyperalgesia compared with healthy controls.

Those with poor pain outcome scores after surgery,

however, showed generalized hyperalgesia and a reduced

CPM response compared with healthy controls. When

patient groups with a good or poor pain outcome were

compared, the poor outcome group also showed lower pain

thresholds, suggesting generalized hyperalgesia. Together

with the negative correlations between VAS score and

pain thresholds/CPM response, these data suggest that the

degree of pain reported by patients with CP after pancreatic

surgery may correlate with the severity of pronociceptive

changes in central pain processing.

Sensitization of the nervous system is a cardinal feature

of most chronic pain disorders33 . Nociception from the

pancreas spreads via local nerves and the spinal cord to

supraspinal structures including the cortex. Changes in

peripheral nerves and the CNS may cause an increase





in nociception and failure of protective mechanisms

to inhibit nociception, resulting in more intense pain

and widespread hyperalgesia9 . Neuroplastic changes in

local nerves and the dorsal horn of the spinal cord

result in increased neuronal excitability, synaptic strength

and neuronal reorganization9 . Subsequently, changes in

supraspinal processing lead to hyperexcitability and firing

of supraspinal neurones at lower thresholds, manifest as

spreading and ultimately generalized hyperalgesia9 . Failure

of systems that depress nociceptive activity (CPM) has

been described for CP34,35 . Such failure is linked to

persistent pain, which is often difficult to manage. All

of these changes, taken together, carry the potential of

independence from peripheral nociceptive input, where

pain and hyperalgesia are no longer driven by peripheral

nociceptive input11 .

Patients with CP who have a poor pain outcome after

pancreatic surgery for pain relief show more aggressive

pronociceptive alterations in pain processing, compared

not only with healthy volunteers but also with patients who

have a good pain outcome. This may be interpreted as a

sign of (relative) independence of central sensitization from

peripheral nociceptive input16 . In these patients it might be

that the source of nociceptive input (the pancreas) has been

treated, but that changes in central pain processing persist,

leading to ongoing pain. This subgroup of patients with

poor pain outcomes is not uncommon in clinical practice,

and is well described36 – 38 .

Based on the theory described above, these patients

should respond best to therapeutic measures targeting

alterations in CNS processing, such as pregabalin for

central sensitization or duloxetine to improve descending

inhibitory modulation20,39 . The present data also suggest

that revisional surgery in patients with CP with poor

pain control is likely to have only limited effects on their

pain. Increasing opioid doses in these patients often fails

and may further enhance hyperalgesia1,8,9 . Although in the

present series there was no difference in opioid use between

the good and poor pain outcome groups, neither was

there a relationship within those groups between opioid

usage and pain detection or tolerance thresholds. This

may simply reflect the small numbers in these subgroup

analyses.

There were reduced differences in pain thresholds for

dermatome C5 between CP and healthy control groups

in comparison with the thresholds in dermatome L4 and

the sum of thresholds. A possible explanation could be the

mix of patients with good and poor pain outcomes in a

single pancreatitis group. Patients with few pain symptoms

showed far fewer QST abnormalities in the C5 dermatome

than those with severe pancreatic pain, thereby increasing

the QST values for the whole group. Once again, this may

simply reflect small numbers in these small subgroups.

Comparison of these results with those for other chronic

pain disorders could be relevant, but caution needs to

be exercised owing to differences in aetiology, disease

progression, symptoms and therapy. A few studies40 – 42

have documented postoperative pain after abdominal

surgery and accompanying changes in CNS processing;

these show that persistent postoperative pain is linked

to a more sensitized CNS. One study43 found that

poorer preoperative inhibitory pain modulation was related

to greater postoperative hyperalgesia and chronic pain.

Persistent pain after breast cancer surgery has been

associated with alterations in CNS pain-modulatory

processes41 , and hypersensitivity on the operated side was

more prominent in patients with chronic postoperative pain

after total hip arthroplasty42 . Future work needs to identify

prognostic factors related to changes in CNS processing

that might then lead to effective strategies preventing pain

persistence after surgery.

Limitations of this study are the retrospective data

collection of patient characteristics and the single QST

measurement after surgery. Prospective data collection and

QST measurements before and after surgery would provide

more complete insight into underlying mechanisms and

processes. Owing to the absence of a control measurement

before surgery, the impact of abdominal surgery alone

on pain processing is difficult to assess and might be a

confounding variable. Inability to determine the presence,

absence or degree of hyperalgesia before intervention is a

further weakness, as this is a feature that can affect chronic

pain treatment outcomes10,15,16 . A prospective longitudinal

observational study of CP during disease progression with

serial QST measurements would provide more insight into

pain processing and how this is influenced by different

therapies16,43,44 .

It is unlikely that the presence of acute on chronic

pancreatitis or local complications after surgery influenced

pain scores, as all patients came from home and were

tested in an ambulatory outpatient setting. No patient had

received or was scheduled for further treatments for any

specific pancreatic or late surgical complications based on

recent imaging.

Technical failure of the surgical procedures might be

a confounding factor. This is unlikely because patients

were specifically recruited where surgeons considered the

operation to have been a technical success. Despite this,

only 18 of the 48 patients had good pain outcome after

pancreatic surgery. This is likely to involve some selection

bias, as only a small proportion of patients with CP were

eligible for the study and those with a poor outcome may





have been more willing to participate in a pain processing

study. Another confounding factor could have been a

difference in treatments between hospitals, but within the

limitations of small numbers there was no evidence for this.

The marked pronociceptive central pain processing

state seen in patients with a poor outcome suggests

that a subgroup of patients has been identified in whom

changes in central pain processing have become relatively

independent of peripheral nociceptive input. The clinical

consequence of this finding is that patients with CP with

poor pain outcomes after surgery should undergo QST,

and targeted drug treatment should be instituted if altered

central pain processing is confirmed. This might involve

ketamine and gabapentinoids for central sensitization,

and tricyclic antidepressants for inadequate descending

inhibitory modulation9,45 . There is early evidence15,20 to

support such an approach, which seems logical based

on monitoring of central processing via serial QST

measurement, as this is generally accepted as an appropriate

method to measure pain processing, is well standardized

and is validated for CP10 .

Identifying patients with autonomous pain processing is

essential to improve the management of pain in CP. These

patients are more likely to benefit from treatments that

target altered central pain processing rather than surgery.

Disclosure

The authors declare no conflict of interest.

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