It’s the Monday from hell. The Monday you will use as your baseline to compare all future Mondays to, and always conclude that it was never as bad as that Monday. It’s a Monday when the code to the door you normally use to enter the hospital has changed, and you are trapped outside as Shrewsbury briefly forgets that it isn’t Antartica. It’s a Monday when the phlebotomists have, for the first time in the history of phlebotomy, decided to do their round before 8am. It’s a Monday which shouldn’t even be called Monday in order to preserve the mildness of the phrase ‘Monday blues’.

You see a 35 year old lady patient with classic cholecystitis. The three key features mention in the BMJ review article are staring you in the face:

1. Tenderness in RUQ (Murphy’s sign being helpful in pointing you away from simple biliary colic and towards cholecystitis)
2. Constant pain in RUQ (at least 12 hours of constant pain according to the same article or at least 6 hours according to emedicine , which distinguishes it from the 1-5 hours of biliary colic)
3. An inflammatory component e.g. raised CRP or WCC, or temperature

This patient has had RUQ pain constantly for 8 hours and is febrile. She hasn’t eaten for 12 hours, and has been sick once. Her WCC is 14.3, CRP 55 and LFTs are all normal. Her pulse is 90, BP 112/80, RR 18, Sats 100% on air and temperature 37.5.

On examination, she is Murphy’s positive. There is no peritonism.

A chest xray shows no free air under the diaphragm.

An ultrasound abdomen is booked for tomorrow morning.

What should we do now from a medical point of view?

It seems people usually keep them NBM and give IV fluids. They often give paracetamol for the temperature/pain and breakthrough oramorph as needed. They often give antibiotics for the cholecystitis.

Antibiotics means “triple therapy” in this trust i.e. gentamicin, metronidazole and benzylpenicillin. This is a broad surgical prophylaxis against anything and everything. I always wondered why we don’t just give a third-gen cephalosporin and metronidazole, as the cephalosporin would cover most bacterial save MRSA, pseudomonas (unless ceftazidime is used), some intracellular bacteria and anaerobes. Of these, only the anaerobes would need to be covered in this scenario, which would be done by metronidazole. It would avoid the resources wasted on gentamicin levels. When the levels aren’t taken, it can fall to the you on call at 11pm to decide whether or not its worse to skip the only antibiotic providing decent gram negative cover versus causing irreversible ototoxicity and nephrooxicity. Whatever answer you decide will be wrong on tomorrow’s ward round. Especially if it’s Monday.

Part of the reason may be to do with C Diff and some extreme fines – about £450,000 per case of C diff over the allowed amount per trust. This may explain why we rarely use co-amoxiclav for anything, and cephalosporins are a collector’s item. I don’t think I can remember the last time I saw clindamycin.

In any case, the suspected bacteria in superinfection of cholecystitis are actually covered by a second-generation cephalosporin alone. According to BMJ Best Practice:

“Antibiotic therapy should include coverage against microorganisms in the Enterobacteriaceae family (e.g., a second-generation cephalosporin or a combination of a quinolone and metronidazole)”

I was finding it difficult to keep making decisions about gentamicin at 11pm. Naturally in a patient with already poor renal function, or in the elderly,  you may err in favour of not giving the gentamicin. You need to balance it up with the risk of the cholecystitis, and I did not know enough to really assess this. I needed to find out exactly why we give antibiotics in cholecystitis.

What normally happens if you don’t give the patient anything?

Cholecystitis if left untreated would usually self resolves in 5-7 days.

Otherwise it may progress through 5 stages:

1. Oedematous – 2 to 4 day, gallbladder tissue is basically intact
2. Necrotising – 3 to 5 days, oedema with areas of haemorrhage and necrosis
3. Suppurative – 7 to 10 days, WBCs present within the gallbladder wall, with areas of necrosis and suppuration. Intra-wall and pericholecystic abscesses may occur.
4. Chronic – occurs after repeated episodes of mild attack (mucosal atrophy and fibrosis of the gallbladder wall)
5. Emphysematous – air appears in the gallbladder wall due to infection with gas-forming anaerobes (usually diabetics)

What do I risk by not giving the patient anything?

If the cholecystitis doesn’t resolve, you risk:

• Necrosis and eventually perforation of the gallbladder
• Gallstone ileus
• Superadded bacterial infection, which can lead to sepsis

Can cholecystitis ever be purely medically managed?

Possibly Grade I, which means “no organ dysfunction and limited disease in the gallbladder; responds to initial medical treatment”.

It is worth emphasising that the ideal management is nearly always going to be surgical.

When do we need surgery?

If Grade I fails to respond to treatment, or the patient is Grade II (no organ dysfunction, but extensive disease in the gallbladder and disease duration more than 72 hours) or III (organ dysfunction), early laproscopic cholecystectomy is preferred. This may be limited by technical difficulty, which may require conversion to open. Alternatively, if the patient is really unwell, a cholecystotomy may be performed, with an interval cholecystectomy at 6-8 weeks.

How does the pathophysiology relate to the principles of medical management?

According to the Tokyo Guidelines:

“In the majority of patients, gallstones are the cause of acute cholecystitis. The process is one of physical obstruction of the gallbladder by a gallstone, at the neck or in the cystic duct. This obstruction results in increased pressure in the gallbladder. There are two factors which determine the progression to acute cholecystitis — the degree of obstruction and the duration of the obstruction. If the obstruction is partial and of short duration the patient experiences biliary colic. If the obstruction is complete and of long duration the patient develops acute cholecystitis. If the patient does not receive early treatment, the disease becomes more serious and complications occur.”

Then, according to the first BMJ article:

“Over 90% of cases of acute cholecystitis result from obstruction of the cystic duct by gall stones or by biliary sludge that has become impacted at the neck of the gall bladder. Obstruction of the cystic duct causes the intraluminal pressure within the gall bladder to increase and, together with cholesterol supersaturated bile, triggers an acute inflammatory response. The trauma caused by the gall stones stimulates the synthesis of prostaglandins I₂and E₂, which mediate the inflammatory response. Secondary bacterial infection with enteric organisms (most commonly Escherichia coli, Klebsiella, and Streptococcus faecalis) occur in about 20% of cases.”

This means that:

1. NSAIDs may be helpful

2. NBM may in itself be helpful. This is because the intraluminal pressure plays a part in driving the inflammatory response. CCK stimulates gallbladder contraction, and CCK release is stimulated by fat containing food. This also explains why the pain can be brought on by fatty foods.

For the initial medical management in general, according to BMJ Best Practice:

“Patients are observed and treated with oral antibiotic drugs or even observed without antibiotics. The pathophysiology of acute cholecystitis is cystic duct obstruction, which causes an acute sterile inflammation. Secondary infection of the gallbladder space by bacteria may follow. Antibiotics are required if infection is suspected on the basis of laboratory and clinical findings. Antibiotic therapy should include coverage against microorganisms in the Enterobacteriaceae family (e.g., a second-generation cephalosporin or a combination of a quinolone and metronidazole); activity against enterococci is not required. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac or indomethacin are recommended as part of the medical treatment for their analgesic effects and their inhibition of prostaglandin release from the gallbladder wall.”

And antibiotics?

According to emedicine:

“The guidelines of the Infectious Diseases Society of America recommend that antimicrobial therapy be instituted if infection is suspected on the basis of laboratory and clinical findings (white blood cell count >12,500 cells/µL; temperature >38.5°C) as well as radiographic findings (eg, air in the gallbladder or gallbladder wall).“

BMJ Best Practice adds on:

“The pathophysiology of acute cholecystitis is cystic duct obstruction, which causes an acute sterile inflammation. Secondary infection of the gallbladder space by bacteria follows. Antibiotics are required if infection is suspected on the basis of laboratory and clinical findings.”

What does this mean for our patient with no gentamicin levels?

I’m not sure. How much of a difference do antibiotics make, if any, given only 20% end up with super-added infection? Risk factors for infection include the duration of the cholecystitis and immunological status of the patient. Without numbers though, it’s hard to weigh things up. Has anyone found evidence of the benefit of antibiotics pre-operatively in cholecystitis?