Question 23

A 54 year old woman was referred to the emergency department by her GP with a 3 day history of vomiting accompanied by upper abdominal pain. On examination she was obese, appeared restless and confused, GCS 13, febrile 38.6 C, heart rate of 100 /min, BP 90/40 mm Hg. She has Spo2 of 88% on oxygen via a non-rebreather bag. There was diffuse abdominal tenderness on palpation in particular in the upper abdomen. Bowel sounds were sluggish. Blood tests taken in a private laboratory the preceding day had revealed a lipase of 400 U/l (normal < 70).

23.1) What are the differential diagnoses of this patient’s presentation?

23.2) What are the causes of hypotension in acute pancreatitis?

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

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College Answer

23.1) What are the differential diagnoses of this patient’s presentation?

1) Pancreatitis
2) Perf DU
3) Intestinal obstruction
4) Acute cholecystitis with sepsis
5) Aspiration and sepsis
6) Gut ischaemia

23.2) What are the causes of hypotension in acute pancreatitis?

a) sequestration (3rd spacing) of protein rich fluids in and around the pancreas and abbdominal cavity, retroperitoneum
b) compounded by pre existing fluid depletion.

c) direct myocardial depression
d) SIRS / sepsis
e) Intra-abd hypertension

f) Bleeding

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

Pulmonary dysfunction - Aspiration, pleural effusions, ARDS, atelectasis.

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

a) Antibiotic use in SAP without overt infection controversial and trial data are conflicting.

b) Antibiotics have been given either IV or IV plus orally/rectally via SDD.
c) Early trials - underpowered, mostly non blinded and included patients with differing disease severity suggested a reduction in both infections and improved outcome with early use of prophylactic antibiotics (Cefuroxime and imipenem) in necrotising SAP when compared with placebo. Subsequent meta analyses including a Cochrane review also suggested that antibiotics reduced infections and mortality and need for surgery in necrotic pancreatitis.
d) 2 recent RCTs (Isenmann 2004 and Dellinger 2007) have however demonstrated no effect on outcome or infection rate when prophylactic antibiotics were used in necrotic pancreatitis. The SCCM (2004) consensus conference on severe pancreatitis recommends against the use of routine prophylactic antibiotics.

Discussion

23.1) What are the differential diagnoses of this patient’s presentation?

An obese hypoxic woman presents in a state of shock, febrile, and with this story of vomiting and abdominal pain. A systematic approach is called for, even though the lipase is high and the obvious single diagnosis is pancreatitis.

Vascular causes:

acute mesenteric vasculitis
mesenteric ischaemia, embolic or otherwise

Infectious causes: sepsis from any origin, but more likely the gut,

biliary sepsis
colitis

Neoplastic causes

perforated colorectal mass
SIRS due to a systemic cytokine release, due to lymphoma or leukaemia

Drug-induced causes

Drug-induced pancreatitis or hepatitis

Autoimmune causes eg. inflammatory bowel disease with perforation

Traumatic causes eg. Boerhaave's syndrome due to excessive vomiting

Endocrinological cause of abdo pain and SIRS, eg. pacreatitis due to any number of causes

23.2) What are the causes of hypotension in acute pancreatitis?

Again, there are several mechanisms:

"Third space losses" due to capillary leak, particularly sequestration in the abdomen
Systemic inflammatory response due to cytokine release
Gastrointestinal losses due to vomiting, diarrhoea, decreased oral intake, and gastric bleeding
Retroperitoeal hematoma (maybe from a ruptured splenic artery aneurysm)
Decreased preload due to abdominal compartment syndrome
Cardiac ouput decrease due to acidosis and SIRS-associated cardiomyopathy

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

ARDS due to systemic cytokine release
Pleural effusions due to third space fluid mobilisation and aggressive fluid resuscitation
Pulmonary oedema due to decreased cardiac contractility and depressed systolic function
Aspiration pneumonia given that the patient has a decreased level of consciousness and presents with a history of vomiting

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

Short answer: there is no role for antibiotics in acute pancreatitis.
In the 1990s, authors were fond of using prophylactic antibiotics because small-scale trials demonstrated a benefit.
These days the evidence does not support the use of antibiotics
Cochrane has an even more recent review which agrees that there does not appear to be any benefit, even on the basis of studies which were not adequately powered to detect a subtle benefit
For some reason, imipenem seems to stand out as an antibiotic which on its own prevents pancreatic necrosis infections. This, again, was the result of an inadequately powered trial.

Again, thank you to Rajkumar (you know who you are) for pointing out the error in this answer. There was a duplication of content from Question 22 of the same paper. Well spotted!

References

Pederzoli, Paolo, et al. "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem." Surgery, gynecology & obstetrics 176.5 (1993): 480-483.

Wilmer, Alexander. "ICU management of severe acute pancreatitis." European journal of internal medicine 15.5 (2004): 274-280.

Villatoro, Eduardo, Mubashir Mulla, and Mike Larvin. "Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis."Cochrane Database Syst Rev 5.5 (2010).

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