Pancreatitis in kidney transplant recipient
66 yo white male had a kidney transplant March 15 because of chronic renal failure due to cystic kidneys and analgetic abuse. He was under treatment with cyclosporin, Crea levels in the high normal range.
Presented to a regional hospital with pancreatitis and was promptly referred to our Medical Department for treatment and ICU care. Initial Ranson was 4, after 48h 3. Stable cardiorespiratory function. Initial Ultrasound demonstrated gallstones with a dilated CBD, an ERCP (with papillotomy) was performed and sludge evacuated.
Laboratory and diagnostic studies
CT-scan could not be carried out with contrast due to elevated Creatinin, demonstrated clear inflammation of whole pancreas and ascites, clear evidence of necrosis can not be affirmed or ruled out (as you all know). CRP is elevated >300 in serial blood tests, Lc 10-13’000.
Patient is afebrile, not intubated, cardiac function stable without pressors. Receives conservative treatment with imipenem and octreoitide. Immunosuppressive treatment with cyclosporin and steroids. I was consulted to see patient.
Suggested MRI to know more about possible necrosis. Radiologist describes patchy necrosis (up to 4mm in diameter) throughout the whole pancreas without larger areas.
What to do now? Immunosuppressed patient with possible(!) necrotizing pancreatitis, stable, not clearly improving.
Literature search does not divulge much information although a very good article by Slakey (Management of severe pancreatitis in renal transplant recepients.) comprising the experience of Milwaukee and Oxford transplant centers suggests good results with early vs. late operation (necrosectomy) in necrotizing pancreatitis for this group of patients.
Treatment
Would appreciate your suggestions and experience.
1. Would you operate and when?
2. What are your regimens of conservative treatment in pancreatitis?
Maybe I missed something, but your description of the patient sounds like he is doing fine! Why do you feel compelled to do something? Afebrile, stabel hemodynamic status, etc–continue in conservative management! Why do you have the patient on antibiotics and octreotide? Neither has ever shown any benefit in pancreatitis, and will only further complicate the course should an infection develop–there is NO prophylactic vaLUE to antibiotics in pancreatitis. It sounds here like the doctors are in worse shape than the patient, running around like a bunch of chickens with their heads cut off, just throwing everything they can think of at him in hopes something might stick.. This is not practicing medicine, but more like volleyball! Just stop the antibiotics and octreotide and continue in your supportive management–the indication for surgery is simple–failure of medical management. If the patient begins becoming septic, THEN operate–by the way, CT has no therapeutic value here so stop getting imaging studies of ANY sort–unless you are now trying radiation therapy!
In essence, the management of this entity in the renal transplant patient should not differ from that in a “normal” patient. A few commandments.
1. In the early (14 days) phase of necrotizing pancreatitits operative treatment is not indicated and hazardous.
2. Beyond the second week do CT-guided FNA for Gram stain and culture. The presence of bacteria signifies infected pancreatic necrosis (IPN) and mandates surgery.
3. In the absence of IPN treat conservatively as long as possible- necrosectomy will be much easier and safer as the necrotic tisue is more demarcated. Before necrosectomy for non infected AP I would wait at least 3-4 weeks- the patient supported in the ICU.
4. There is some level 5 evidence that entral nutrition- transpyloric- is betetr than the usually given TPN.
5. The operation when performed should be tailored to the extent of pathologic process found. For minimal necrosis/IPN local debridemnet + drainage abdominal closure (“Warshaw’s method”) is appropriate; some people -especially your friend Begger from Ulm- would add local lesser sac lavage.
For extensive necrosis/infection- planned relaparotomies ala’ Ed Bradely should be considered. The coexistence of intra-abdominal hypertension in these cases should not be ignored-and laparostomy methods should be adopted.
About the somatostatin you are right- but on the antibiotic issue you may be wrong. SEVERE acute pancreatitis (i.e. APACHE II >8, Ranson criteria >3, presence of necrosis on CT scan) is an indication for antibiotic prophylaxis. This has been supported by randomized prospective studies. The aim of the antibiotics in such cases is to prevent superinfection of the necrotic tissue. Sterile necrosis can be dealt with by the host’s macrophages -usually, infected necrosis can be removed only with the knife.
An extract from a chapter by John Bohnen: Peritonitis-AB management . In:
Crucial Controversies in Surgery.
Acute pancreatitis
In the past, a number of studies had shown that antimicrobial therapy had no benefit in the management of acute pancreatitis. Antibiotics were therefore only recommended as adjuncts to surgical therapy, when operative debridement or percutaneous drainage is performed. However, three recent studies, using imipenem, cefuroxime and selective gut decontamination respectively, have shown fewer instances of peripancreatic infections (called”pancreatic” in two of these papers) and deaths.
The imipenem study prospectively and randomly allocated patients with pancreatic necrosis (determined by CT scan) to receive either intravenous imipenem for two weeks, or standard medical treatment without antimicrobial agents. The imipenem-treated group went on to develop “pancreatic sepsis” in 12% of cases vs 30% of cases in the control group. No difference was found in mortality rates. Although these results suggest that imipenem prophylaxis was beneficial, the study had important methodologic limitations. Only 74 patients at six centers were included in the study, too small a sample size to detect differences in mortality (there was a slight trend to fewer deaths in antibiotic-treated patients) or adverse effects. Colonization or superinfection with antibiotic-resistant organisms was not reported. Although patients were randomized, the clinicians were not blinded to which treatment patients received, and no placebo was used. Although it was reported that patients with infected pancreatic necrosis underwent operation, the indications for diagnostic aspiration for culture and operation were not clearly stated. Terms such as “sepsis” and “multiorgan failure” were not defined. In another single center study, patients with alcohol-induced necrotizing pancreatitis (determined by CT scan) were randomized to receive standard treatment without empiric prophylactic antimicrobial therapy in one group vs intravenous cefuroxime that was given to patients in the other group until clinical recovery or normalization of C-reactive protein concentrations. The antibiotic-treated patients had significantly fewer deaths and infectious complications, which consisted of mainly infected pancreatic necrosis and central venous catheter infections. Staphylococcus epidermidis was the predominant pathogen in both the vascular catheter infections (as expected) and in infections in the region of the pancreas, an unusual finding. The study had methodologic problems. Only 60 patients were included and no placebo control was used. Operative management was not standardized. The choice of cefuroxime and predominance of S. epidermidis as a pathogen was unusual: the organisms most commonly isolated from pancreatic infections in other clinical studies have been E. coli, other gram negative rods and Enterococcus species. In a recent controlled, randomized, multicenter clinical trial, selective digestive decontamination (SDD) was compared to standard care for patients with severe acute pancreatitis. Patients in the SDD group received oral and rectal colisitin, norfloxacin and amphotericin until clinical recovery, plus intravenous cefotaxime until gram negative bacteria were eliminated from the mouth and rectum (actual duration not specified). Patients given SDD had a trend to reduced mortality, which became statistically significant after adjustment for severity of illness by multivariate analysis. There were significantly fewer pancreatic infections and laparotomies in the patients treated with SDD. Interestingly, of the patients who developed infected pancreatic necrosis, nine out of nine in the SDD group and 12 out of 20 in the control group harbored S. epidermidis in the peripancreatic region. This study, too, had methodologic problems: a sample size of only 102 patients, lack of clinician blinding to treatment regimen and lack of control for surgical intervention.
It is difficult to draw conclusions from the studies cited above. Although there were problems with research methods, all three clinical trials did show improvements in outcomes in patients treated with antibiotics. Until properly controlled, double-blind studies are performed, something that will take major effort and cost, the clinical decision to use antibiotics in pancreatitis will depend as much on philosophy as on sound evidence. Weighed against the possible benefits described above are the added costs of antimicrobial administration, and risks of adverse effects and resistant organisms.
The role of S. epidermidis in peripancreatic infections is not clear, either. Contrary to the previously reported predominance of enteric organisms, presumably having translocated from the gut, recent findings of staphylococci in the infected retroperitoneum implicate infected intravascular devices as etiologic sources. This could point to an infection control problem that could further confound the interpretation of clinical trials in this confusing area. To account for variations in patient profiles and the broad array of treatment practices among centers, large, multicenter, double-blinded clinical trials will be needed to resolve the antibiotic controversy. Cost and differences of opinion regarding surgical practice will make this difficult to accomplish.
Wow…a rather rough reply but…well. The only thing that worries me is that the pt must continue with his immunosuppressive therapy and ,only for that reason,I think that ABs should be maintained as well as IPP ’cause of the risk of UGD bleeding.
Altho your motivation is understandable to place on antibiotics, there is still no defendable justification, and until we start acting like physicians, rationally using antibiotics when there are proven indications, we will continue inflicting on the world the ever-spiraling costs and dangers of antibiotic resistance–which, by the way, kills people! And–as is so evident in these posts, doctors are the sole cause of this very avoidable problem–so doing this to make ourselves feel better is not rational or morally defensible, and we need to stop acting as if the world revolves around us!
I’m sorry but the study you quoted shows no such thing, with the flaws I noted when I read it some time ago–it actually says no more than “we used it and they seemed to work fine”–also, you are confusing treatment with prophylaxis here–the advanced septic stage certainly requires antibiotics for treatment of established infection–but we were taliking about uncomplicated pancreatitis, in which setting a number of studies have established that there is no prophylactic value to antibiotics in reducing the incidence of subsequent infection, and in fact they make any subsequent infections harder to eradicate! The case presented showed no evidence of being anything but uncomplicated pancreatitis, with no indication of infection at all, and that is where I directed my comments.
I was actually trying to touch the point and which was referred to and also (as usual) academically and poignantly answered:
– Does this (or for that part any other) patient who has immunosuppressive therapy due to his kidney-transplant (or other organ transplant) need a special approach to pancreatitis, which seems to be severe, possibly necrotizing?
I totally agree to your arguments regarding octreotide (not Somatostatin). There is certainly no firm evidence to support that treatment, although there also are groups trying to perform studies to show otherwise (i.e. Paran H. et. al.: “Preliminary report of a prospective randomized study of octreotide in the treatment of severe acute pancreatitis” J Am Coll Surg). Our patient is on the Medical ICU treated by the gastroenterologists, who have taken the decision to decided to treat with octreotide. BTW is there anybody else out there who treats their patients with pancreatitis with octreotide?
Regarding antibiotic prophylaxis(!) I take he’s side, specially in an immunocompromised patient. I cannot quote any further studies. I think the points regarding this matter have been made or will come up during further discussion.
I would also agree that (contrast enhanced) CT has no “therapeutic value” in pancreatitis, I’m also not aware of having made that point! It usually is a “diagnostic” procedure and currently is the standard imaging procedure to help differentiate edematous from necrotizing pancreatitis. Although you do not implicitly state so I am sure you also use it for that purpose. I am also not aware of the fact that MRI has a “radiation” potential!
Now please answer a simple (humble) question without the usual flak: – Do you treat your immunocompromised patients with severe pancreatitis differently from “normal” patients?
The quoted paper (from Tel Aviv) was awful! The guys never even tried to stratify their patients. I remember wondering why on earth the Editors of the JACS accepted such rubbish.
In fact, Warshaw and his group from the MGH published in the recent issue of Ann Surg that MRI may be safer in severe AP since the contrast-enhanced CT may damage the already compromised pancreatic micro-circulation- producing more necrosis.
No, unless there is some evidence about which I amunaware to support such an approach–and your question to the group is on the wrong track–it should not be “who else does this”, as people out there do all sorts of things–the real question is “what support is there for doing something different in these patients than other human beings”–I appreciate your reply, and no offense was intended, as I realize it was your internists applying these Rx’s.
Now you’re suggesting that AB might be prophilactic in the secondary infection of necrotic pancreatic tissue. And in your quotes,S. Epidermidis appears to be one of the baterias that have been isolated. Really queer.
Thought that this bacteria was normally found on the skin and in certain specific parts of the body…
Can’t imagine how did they get into the blood stream and then contaminated the necrotic pancreas unless thru vascular accesses used for hydration, TPN,etc.The ones who worked this stuff should be more careful when they perform a high venous flow punction with catheter installation. Is this the way cientific research is being conducted?
Up to my knowledge, necrotic pancreatic and peripancreatic tissues are almost avascular, because of the necrosis ans subsequent isquemia or viceversa….who knows?…. You think ABs could reach at effective concentration levels into the focus and prevent secondary infection?
You might be treating bacteremias of different origins, yes, you might, but you’re not exercising any septic protection over the necrotic areas.
The choice of the ABs to be used,as you tell us, has nothing to do with the commonly bacterias isolated from a pancreatic and/or peripancreatic infected tissues, except imipenem, partially and cefuroxime,partially.
Should we use prophilactic ABs, the adequate ones, in front of severe necrotic pancreatitis as a routine part of the medical measures from the beggining or should we continue accepting that the use of ABs in this phase doesn’t modify at all the outcome and septic complications may appear as well even if you employ or do not employ prophilactic ABs?
And this question is really important to be answered as it might make us all start thinking to modify our therapeutic cryteria in front of severe acute necrotic pancreatitis.
Perhaps I’m wrong….who knows?
You use a lot of words bla, bla, bla but you do not bring any evidence.
Now I quoted here a lot of experimental and clinical data to suggest that AB are useful prophylactively in selected patients with severe acute pancreatitits. Do you have any solid data to prove otherwise?
How bacteria get into the necrotic pancreatic tissue? Gut bacteria and fungi get there by TRANSLOCATION from the adjacent transverse colon- this has been nicely shown in experimental studies. Other bacteria- as you suggested may be arriving at this site form lines and other entry site needed to support the critically ill patient.
Studies showed that Imipenem penetrates best the pancreatic tissue. You may continue bla bla bla about Hamlet and throw words: the experts in this field however concluded that prophyalctic AB are indicated in severe AP. I use them to prevent my NP patient become IPN.
You are too harsh on H. who is trying to act in the patient’s best interest. There aren’t enough immunocompromised patients with severe pancreatitis that have been studied for this question of antibiotic prophyllaxis in severe pancreatitis. However, I’m sure you have seen them develop other infectious complications frequently and they are unusually silent in their clinical manifestation. I too would treat the patient with Imipenem. NOT to make myself feel better, but to err on the side of the patient’s safety. The world should not revolve around us but around our patient. That is our focus. It would be nice to have a big prospective controlled randomized study to point to saying there is no difference in these immunocompomised pancreatitis patients but until that time I’m for treating them differently than the “usual” pancreatitis.
I am certainly not impugning your motives in this practice, only their validity–pancreatitis is not an infectious process, but a chemical inflammation. I wonder how many such patients will go on to develop C. difficile enterocolitis and resistant IPN which you will then conveniently overlook as just the price that has to be paid for treating yourself–I suppose you also “treat” with octreotide, another thing that has come completely out of someone’s imagination because it sounds like it should be right. Also, you are not the one having to pay for these practices out of your own pocket like the patients you are so concerned about.
I don’t use antibiotics in pancreatitis probably mainly because if they are that severely ill, I would seriously consider transferring them for tertiary care. Now, I did end up operating on an elderly patient with infected necrotizing pancreatitis last year, because her surgeon went on vacation and I almost immediately got called to see her and it seemed like an emergency at the time (probably was, high fever, high white count, tachycardia)—luckily, she survived. She did, of course, get antibiotics after surgery.
However, as far as the issue of antibiotics causing antibiotic resistant bacteria, I think the primary culprits are the primary care doctors who give in to all the patients and parents who want antibiotics for viruses. We have had the usual and worse than usual winter upper respiratory viruses and most of these people who have seen local doctors have gotten Zithromax (one of the new more expensive macrolide antibiotics). I just saw one of these patients (42 year old non-smoking otherwise healthy male) who had an even longer than usual nagging scratchy throat and cough, finally after multiple courses of antibiotics over 1 month, put on steroids and came in massively distended with cramping abdominal pain. His X-rays showed dilated small bowel but even more dilated colon down to his rectum. He was not vomiting and had had some diarrhea a few days before. I suggested that this was probably Clostridium difficile enterocolitis and started metronidazole and he was much better by the next morning.
Anyhow, the numbers of patients treated inappropriately with antibiotics for viral upper respiratory infections far outweighs the number of patients treated inappropriately with antibiotics for pancreatitis (not that we shouldn’t weigh the current evidence and avoid antibiotics where appropriate–I, too, see general surgeons giving 2 week courses of IV antibiotics–who knows what for, theses are the same general surgeons who use TPN exclusively and almost never feed enterally).
Pancreatitis in a transplant patient on steroids (the biggest problem) is a bad disease. Worse the pancreatitis in other populations. There is not a lot of data on the management since it is not too common. However we general assume the same rules apply as to non-transplant patients. No enteral feeds (although some recent data suggests that is not problem) but good nutrition support. Without evidence of infection we generally do not use antibiotics, and we do not use octreotide because we think it helps little and is expensive.
I would have a hard time operating on someone who is as you described stable and with patchy necrosis on the MRI scan. I am not sure what you would do to make him better.
With regards to the renal disfunction, we would probably stop or dramatically decrease the dose of cyclosporine. It is unlikely that he would reject in this very sick state.
The most important thing to keep in mind is that the kidney should not be a concern. If you over treat with immunosuppression to “save the kidney” you may kill the patient. If the patient survives but the kidney is lost from rejection, you can either dialyze or retransplant.
There is no data to treat transplant patients in a manner other than how non-transplant patients are treated but they probably do worse secondary to the immunosuppression. The main rule to follow is (talking here almost only about a non-life sustaining organ such as the kidney).
The way we treat and monitor Severe Acute Pancreatitis with necrosis is as follows :
1.- All the general medical measures known by all of us.
2.- NG tube for gastrointestinal decompression until ileus, if present, relieves. We don’t think that gastric secretions might modify the outcome of an acute pancreatitis as we believe that the debut of such a pancreatitis has a fatal way of evolving.This means that an edematous or interstitial pancreatitis will remain as this and won’t change to necrotic or haemorraghic form of presentation.
3.- Protect the existing risk of UGD bleeding with H2 blockers.
4.- We don’t use neither octreotide nor AB in this stage of evolution.
5.- In all severe pancreatitis, we use TPN. As soon as ileus is alleviated and no other contraindication is present, we start enteral nutrition through a nasoyeyunal catheter.
6.- We scan the patient once a week at least in search of imagenologic changes that might let us know that pancreatic and peripancreatic collections are developing.We follow the Balthazar-Ranson classification.
7.- If the pt develops clinical, gasometric and haematological signs of sepsis, we proceed to perform a percutaneous punction guided by US or scanner.The aspirated fluids are submitted inmediately to bacteriological cultures and Gram.If what has been punctioned is a collection, we leave in place a pig tail drainage and we repeat the procedure in order to drain 2 or 3 or more collections if necessary.
8.- AB therapy is started usually with a third generation cephalosporyn and Clindamicine or Flagyl, due to the suspected pressence of anaerobic gram (-) bacterias.Changes are made when bacteriological results are available.
9.- If, in spite of percutaneous drainage and antibiotherapy, the septic condition persists, we consider necessary to take the pt to OR.
There was a time when studies showed that Cipro best penetrated pancreatic tissue. But is there a study to show what antibiotic best penetrates all the necrotic tissue?
Would you please tell me how can antibiotics penetrate pancreatic necrotic tissue as we know that it’s condition is avascular and isquemic?… This is based in level evidence 1 as it needs only to take a look to a hystological prep of NPT to be sure that vascularity is absent and isquemia is present.
My point exactly.
It is amusing how you cry on each others shoulders-hugging each other for some mental support in this harsh world of reality.
The problem with you is that you are not serious! You will discuss a topic- on and on and on and on-, letting us have your private wisdom but you do not prepare yourself for the discussion as an academician should do. And you are an academician judging from your title.
You will lecture us about pancreatitits & antibiotics and Hamlet without doing any home work. Yes, I know that you read Hamlet every other day- but you did not read anything recently written about antibiotics and pancreatitits. Reading a title or an abstract is not enough- before commenting with such a great authority on a subject- in such an international forum- go to the library- get out all what was written and read. And only then comment.
There is an entity called mis-information and demagogy-very easily spread in a democratic and not peer-reviewed forum.
So professor – you may be right that antibiotics won’t penetrate into the center of pancreatic necrosis- but this is not the rational for antibiotics in PN. When the necrosis is infected -antibiotics won’t work. The rational of using AB is to PREVENT the infection- to prevent the bacteria arriving from the colon and IV lines to the necrosed pancreas.
When you buy red wine you can prevent it from becoming acid by storing it in your celler- you can not make it better when it is acid. The same with your pancreas.
I can tell you that we treat around 100 acute pancreatitis per year…How many do you treat?…not read….Perhaps, I wonder, if you during all the time you have been wandering around the world, from place to place, witout making roots, you have ever seen such a quantity…But you speak always ex cathedra, based on papers you read…I remain wondering, how many cases you have treated in reality?
Sometimes,you attack fiercely the use of prophilactic AB, give us a lot of literature support, and sometimes you state also fiercely, as now, that AB can and should be used as prophilactic measure.Who can guess where do you want to go?
I know you like good wines, but this last statement for me is not applicable to the matter we were discussing….And drinking it, might lead you to a pancreatitis and then we’ll see if you’re consequent with your readings and plea to your attending surgeon to give you AB in spite of the complications that can be derived of the misuse of such a therapy.