Pancreatic ketoacidosis-a rare case report

Euglycemic Pancreatic Ketoacidosis is a syndrome of high anion gap acidosis in which the high anion gap is due to elevated serum ketone bodies comprising of acetone, acetoacetate and beta hydroxyl-butyrate, due to increased peripheral adipose tissue breakdown by elevated serum lipase as a consequence of acute pancreatitis with normal blood glucose levels. There are multiple causes for ketonuria and/or ketonemia with or without acidosis like uncontrolled diabetes mellitus, usually of the insulin dependent type (diabetic ketoacidosis), lactic acidosis, prolonged starvation (starvation ketosis), ethanol ingestion (alcoholic ketoacidosis), sepsis, pregnancy and vomiting. Our patient was not a known diabetic and his blood glucose were always within normal limits, so this ketoacidosis cannot be attributed to Diabetes Mellitus. It cannot be attributed to starvation as our patient was not fasting when he got admitted and furthermore ketoacidosis is not a frequent manifestation of starvation adding to it that we transfused adequate amount of DNS and resumed oral intake during our observation period. It cannot be attributed to vomiting as our patient had only two episodes of vomiting. Our patient does not have any liver or kidney pathology and there is no history or evidence of alcohol intoxication. But, acute pancreatitis without diabetes-mellitus, causing ketoacidosis is a very rare presentation which is caused by high levels of pancreatic lipase in the circulation.


Introduction
Our patient was not a known diabetic and his blood glucose were always within normal limits, so this ketoacidosis cannot be attributed to Diabetes Mellitus. It cannot be attributed to starvation as our patient was not fasting when he got admitted and furthermore ketoacidosis is not a frequent manifestation of starvation adding to it that we transfused adequate amount of DNS and resumed oral intake during our observation period.
It cannot be attributed to vomiting as our patient had only two episodes of vomiting. Our patient does not have any liver or kidney pathology and there is no history or evidence of alcohol intoxication. Eckerwall G et al, advocated a nutritional treatment regime in severe acute pancreatitis including a moderate and hypocaloric initial fluid resuscitation, parental nutrition as the preferred route for nutritional support and a non-strict glucose control, with an associated mortality of 17%, indicates several modes of improving outcome [1].
In his report, Kabadi UM described three patients who manifested ketoacidosis at the time of presentation of acute pancreatitis. In none of these patients could ketoacidosis be attributed to any of the well-known pathogenetic factors such as ethanol, diabetes mellitus or prolonged starvation Therefore, he believe that pancreatic ketosis or ketoacidosis may be a distinct syndrome with ketogenesis being promoted and maintained by extremely high circulating pancreatic lipase concentrations. This was thereafter named "Kabadi syndrome", mimicking diabetic ketoacidosis [2,3].

Case Report
A 13 years boy, known case of recurrent pancreatitis was admitted in ICU with complaints of acute onset severe upper abdominal pain, radiating to back which got mildly relieved by sitting up or stooping forward along with two episodes of bilious and nonprojectile vomiting. There was no history of fever, starvation, sepsis, alcohol intake or any liver or kidney pathology. On examination patient was conscious, oriented but irritable, afebrile, dehydrated and dyspnoeic. Pulse rate was 116/min; blood Treatment: We made a clinical diagnosis of acute pancreatitis with ketoacidosis. We kept the patient nil per oral for 12 hours and we started oral liquid diet after that along with pancreatic enzyme replacement of 10,000 units thrice daily. We treated him with DNS infusion at the rate of 100ml per hour and intra-venous insulin infusion; Intra-venous infusion of dexmedetomidine at the rate of 0.2 microgram per kg per hour was started for abdominal pain which was slowly tapered off in the next 24 hours according to the patient's symptoms. Four hourly monitoring of blood glucose, vitals and input-output charting was done (Table  1). Every 4 hourly arterial blood gas (ABG) analysis was done. After 24 hours hemogram with complete blood counts, serum electrolytes, Liver function test, serum creatinine, blood urea, plasma ketones and urine ketones were repeated ( Table 2).  Hurrell FE et al studied Beta-hydroxybutyrate concentrations in dogs with acute pancreatitis and without diabetes mellitus. They also found the same phenomenon occuring as pancreatic lipase was responsible in induction of ketonaemia by promoting ketogenesis via peripheral adipose tissue breakdown, without the blood glucose being high [9]. Kabadi described a syndrome, "pancreatic ketoacidosis" or the presence of ketonaemia in association with acute pancreatitis. In these patients, hyperglyca emia was not characteristically noted. In his report, he describe subjects in whom ketoacidosis was detected at the time of presentation with acute pancreatitis. Both of these subjects manifested simultaneous mild hyperglycaemia.
There was no prior history of diabetes mellitus, nor did he require antidiabetic therapy following resolution of acute pancreatitis. In none of these cases, ketoacidosis could be attributed to diabetes because ketonaemia persisted for several days despite attaining euglycaemia with insulin therapy in one and with appropriate therapy for acute pancreatitis in the other contrast to diabetic ketoacidosis (DKA) in which ketonaemia resolves within 48-72 hours. Ketoacidosis could not be attributed to ethanol either because serum ketone titers are frequently negative in this syndrome and ethanol was not an inducer of pancreatitis in one of the subjects. Finally, starvation as a cause was least likely since starvation induces ketonuria rather than ketonaemia and hardly ever acidosis. Finally, mild hyperglycaemia has been documented to occur in acute pancreatitis. In addition, serum ketone titers declined in concurrence with lowering of serum lipase levels and became undetectable only following near normalization of serum lipase suggesting that circulating elevated pancreatic lipase level may have contributed to enhanced adipose tissue break down causing ketoacidosis. Therefore, it is believed that ketoacidosis occurring with acute pancreatitis or pancreatic ketoacidosis may be mistaken for diabetic ketoacidosis [10][11][12].
During our treatment as the episode of pancreatitis started to settle down as evidenced by decreasing serum lipase, the ketoacidosis also started to decrease. By the end of 24 hours there were no ketone bodies in plasma and urine; the blood pH and anion gap returned within normal limits and the abdominal pain had settled. During all this duration his blood glucose were always within normal limits (Table 1,  Table 2). Hence in our case it is very clear that acute pancreatitis was itself responsible for this ketoacidosis and it resolved when the patient recovered from the disease.

Conclusion
Euglycemic KA thus poses a challenge to physicians, as patients presenting with normal BG levels in ketoacidosis may be overlooked, leading to a delay in appropriate management strategies. Despite euglycemia, ketoacidosis in patients remains a medical emergency and must be treated in a quick and appropriate manner.

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