Acute pancreatitis: Translating science to clinical practice in early illness

Though this sounds more technical than other articles in this blog, I would like my blog visitors to understand the challenges of treating acute pancreatitis. Acute pancreatitis is a challenging disease, that can potentially kill a patient. When I started treating acute pancreatitis independently in 2001, at PRS Hospital, Thiruvananthapuram, I had very little access to information that is available on pancreatic disease management that is easily available now a days. A look at the statistics of death due to acute pancreatitis revealed that multi organ failure was the chief cause of death in acute pancreatitis.

I set out very simple goals that can prevent circulatory failure and renal failure and allowing early feeds - treatments which are standard at this time.

The first 24 hours in acute pancreatitis reveals an insurmountable obstacle in that most of the inflammatory activation is complete by the time of presentation.
The role of the treating doctor is to prevent the second hit that can lead to multiorgan failure.
It is this change of goals that enabled us to have excellent results in acute pancreatitis.

Antiprotease treatments and prevention of macrophage activation are experimental goals that drives research in acute pancreatitis and will take a while to achieve success and translation into clinical practice. My focus has been on reducing microcirculatory damage in acute pancreatitis. Sluggish blood flow in the pancreatic microcirculation leads to pancreatic cell damage due to ischemia. These ischemic cells also may release contained enzyme packets into the pancreatic interstitium. With the availabilty of active trypsin in the neighbourhood, it is like pouring petrol on fire.

The three key physiological alterations in acute pancreatitis.
Proteases are enzymes secreted for digestion of proteins.
Microcirculation is a term that broadly denotes capillaries that serves as outposts where fluids are exchanged at tissue level.
Macrophages are cells that are involved in destruction of foreign cells and bacteria.

 Most of the patients I audited, in Thiruvananthapuram as well as in Chennai, had only one major treatment miss - not giving adequate fluids. Most of the consultants were very busy or felt that acute pancreatitis is easy to treat. Glaring gaps in volume rescue was noted in that physicians prescribed a standard volume of fluids for all patients with acute pancreatitis, regardless of the patient need and organ function.

We set out to correct this by matching the fluid needed to the fluid that is given in the first 24 hours, by predefining the goal. The goal was the reversal of tissue acidosis. Reversal of base deficit was the first goal that we changed compared to other teams. I am not aware of any other team that uses this criteria. Drop in hematocrit or a drop in BUN occurs with adequate resuscitation and other teams in India have used urine output of 0.5ml/kg/ hour as goals for acute pancreatitis. Such goals serve as surogate markers in acute pancreatitis. It is our experience that urine outputs of 1ml/kg/hour serves well during the initial 24 hours following admission and we are aggressive to chieve this clinical goal and monitor for reversal of base deficit. This is similar to burn resuscitation and the end point of a successful resuscitation in burns, using Ringer's lactate is mild metabolic alkalosis. Again, this experience comes from treating large burns to which acute pancreatitis is similar.

This base deficit reflects tissue acidosis and predicts multiorgan failure. We know that most of the death in the early phase of acute pancreatitis is due to multi organ failure. Our premise was that, if we are able to disconnect the chain of events that promote MOF, one can succeed in getting good results in these patients. The second premise by which we used the same criteria, was that adequate fluid resuscitation reduces ichemic damage to pancreatic acinar cells leading to less enzyme leak, less enzyme activation.

Fluid resuscitation goals in acute pancreatitis - existing goals and our goals

In 15 years, that I have used this protocol, I have never had to refer a single patient to any other hospital for care and have lost one patient due to multidrug resistant Klebsiella, that the patient picked while on treatment in another hospital. I am not writing this to boast of any better result, but only to highlight that paying attention to simple details of medical care actually translates into improved patient results. We evolved a check list protocol for acute pancreatitis, that simplified this treatment so that it can be continuously monitored by our specialised nursing team. I am not able to give further details as this is getting ready for academic publication.

The second glaring defect or over kill in acute pancreatitis is the use of antibiotics. In Chennai, this is a phenomenon, with every pancreatitis patient being treated with Meropenem. It is told that the patient is started on "higher antibiotics", when it is not actually needed. Most of the patients in our treatment do not receive antibiotics as they have never needed it. I prescribe antibiotics to patients with clinical sepsis or patients with pancreatic necrosis. As far as antibiotics are concerned, we keep it simple. It is not needed, unless I define the indication in the given patient.

Early feeding is the next key step in acute pancreatitis. Feeding must commence when fluid resuscitation is complete. Any feed is good as long as the patient tolerates it. We have never used formula feeds more than a day. It is easier for our patients to tolerate easily digestible home made foods and allows them to scale up as they feel better. Our feed time is usually within the first 48 hours and we usually discharge patients on day 4, once the necrosis evaluation is complete.

There are 2 peaks that are noted in deaths from acute pancreatitis. The first peak is in the first week after diagnosis, estimated to be roughly 30% and the second peak is in the 4th week, which again is in the 30% range. There are lots of teams presenting patients on pancreatic necrosis during clinical conferences, which surprises me. I am of the belief that if you prevent MOF by adequate resuscitation in the eraly phase, it will also mean less number of patients that have pancreatic necrosis. While the numbers will never reach zero, it will mean less burden on society.

It has been my focus in the treatment of this disease that if you get the patient out of MOF and reduce necrosis by good fluid resuscitation, the challenges of infected pancreatic necrosis and infective deaths falls into insignificance. So far, my experience with this disease tells me that I am on the right path. Only hard data will tell me better things.