BCM Gastroenterology Grand Rounds - Discussion
| Final Diagnosis: Severe malnutrition secondary
to chronic pancreatitis and severe metabolic stress, followed by refeeding
syndrome |
| 1. Metabolic deficiencies in chronic pancreatitis |
|
Weight loss is the most common metabolic derangement
in chronic pancreatitis. Many patients initially compensate
for their poor absorption by increasing their intake (polyphagia);
however, reduced intake in patients with chronic pain or continued
alcoholism, steatorrhea, and uncontrolled diabetes eventually leads
to weight loss(1). Metabolic deficiencies in chronic pancreatitis
reflect pancreatic exocrine and endocrine insufficiency: Maldigestion and steatorrhea in chronic pancreatitis
are treated with pancreatic enzyme replacements. 30,000 units
of lipase with each meal is usually sufficient to treat steatorrhea.
Failure of steatorrhea to respond to enzyme replacement therapy should
prompt the following measures: 1) ensure the proper dose of enzyme,
and increase the dose to above 30,000 units of lipase per meal if
the response is still insufficient; 2) change to a nonenteric-coated
preparation with acid supression as protection, as enteric-coated
preparations may release their contents too distally for efficient
digestion and absorption; 3) consider other derangements contributing
to maldigestion and malabsorption, such as small bowel bacterial overgrowth
or gastroparesis (which can be seen in patients with chronic pancreatitis),
or 4) replace dietary fat with medium-chain triglycerides, which do
not require lipolysis and micelle formation for absorption (2). Endocrine insufficiency |
| 2. Monomeric/oligomeric diets in chronic pancreatitis |
| Monomeric formulas, otherwise known as "elemental"
diets, supply nitrogen in the form of free amino acids, carbohydrate
as glucose polymers, and minimal amounts of fat as long-chain triglycerides.
An example of this is Vivonex Plus, which provides protein as
free amino acids, carbohydrate as maltodextrin and modified corn starch,
and fat as soybean oil (a long-chain triglyceride) (Visual 1). Oligomeric formulas, otherwise known as "semi-elemental" diets,
provide nitrogen as hydrolyzed casein, whey, or lactalbumin, containing
different lengths of small peptides. Oligomeric formulas have
a theoretical advantage over monomeric formulas because dipeptides and
tripeptides have specific small intestinal transport mechanisms and
are absorbed more efficiently than amino acids or whole protein (3).
Both diets in turn might have a theoretical advantage over standard
polymeric formulas consisting of whole proteins in patients with pancreatic
exocrine insufficiency. The direct effect of monomeric/oligomeric
diets given to patients with chronic pancreatitis is unclear. Keith
studied three patients with chronic pancreatitis who had pancreaticojejunostomies
and T-tubes inserted into their pancreatic ducts from which pancreatic
secretions could be collected (4). He showed a decrease in pancreatic
secretory pressure and volume in patients given a low-fat elemental
diet via a nasogastric tube (Visual 2). This finding may have an implication
for the use of monomeric/oligomeric diets in patients with chronic pancreatitis
who have intractable pain despite the use of pancreatic enzymes. More
relevant to the issue of malnutrition, another study evaluated six nutritionally
stable patients with total pancreatectomy who each underwent two periods
of nasogastric enteral nutrition identical in all respects except for
the nitrogen source -- intact lactalbumin or its hydrolysate (5). All
patients had greater nitrogen absorption with lactalbumin hydrolysate
than with lactalbumin (Visual 3). However, nitrogen balances during the two periods of enteral
nutrition were not signifcantly different because urea production rate
was greater with lactalbumin hydrolysate than with lactalbumin. Plasma
concentrations of proteins and amino acids (except threonine and lysine)
did not differ significantly during the two periods (Visual 4). The implication is that oligomeric/monomeric diets provide
no advantage over polymeric diets in maintaining positive protein balance.
However, these findings may not be applicable to patients in unstable
nutritional and metabolic condition. |
| 3. The refeeding syndrome |
| The refeeding syndrome occurs when severely malnourished
patients are fed with high carbohydrate loads, either from high-carbohydrate
enteral feeds or glucose-based parenteral formulas. The delivery
of glucose can cause a large increase in the circulating insulin level,
which in turn can cause fluid retention and rapid uptake of phosphate,
magnesium, and potassium into cells. Fluid retention can lead
to acute heart failure especially in the context of chronic malnutrition
and atrophic cardiac muscle with reduced stroke volumes. In addition,
increased CO2 production and O2 consumption from
renewed anabolism can lead to increased minute ventilation and difficult
weaning from artificial ventilation. Hypophosphatemia can also
cause respiratory and cardiac failure and arrhythmias and should be
monitored very closely during the early period of refeeding. Furthermore,
the gut atrophies and the production of digestive enzymes decreases
with severe malnutrition; the return of enteral feeding may therefore
be initially poorly tolerated by the unadapted gut, resulting in nausea
and diarrhea. Because of the risk of refeeding syndrome in patients with severe malnutrition, a cautious approach is advocated during the first week of refeeding (6). Daily caloric intake should be approximately 15 to 20 kcal/kg, containing approximately 100 g of carbohydrate and 1.5 g/kg of protein. Fluid intake should be limited to approximately 800 mL/day plus maintenance for insensible losses. Sodium should be limited to approximately 60 mEq per day, but phosphorus, potassium, and magnesium should be replaced liberally. Daily monitoring of body weight, fluid intake, urine output, and plasma glucose and electrolytes is essential during the first week of refeeding so that appropriate nutritional adjustments can be made. Weight gain above 0.25 kg/day or 1.5 kg/week probably represents fluid retention. Our patient was admitted with protein-calorie malnutrition from severe chronic pancreatitis. About three weeks into his hospitalization, during which time he had 12% weight loss, the patient was begun on Choice DM tube feeds at a peak rate of 85 mL/hr. It is doubtful that he was receiving tube feeds consistently as he had approximately 50% weight loss in the next month, which was accelerated by severe metabolic stressors (sepsis, adrenal insufficiency, acute respiratory failure, etc.). His nadir BMI was 8.4 kg/m2 (BMI less than 13 for men and 11 for women is thought incompatible with life). He developed profound muscle weakness, including likely respiratory muscle weakness which made it difficult to wean him from artificial ventilation. After PEG tube placement on 5/18/04, his feeds were switched to Vivonex Plus, given the possibility of maldigestion from chronic pancreatitis. Over the next week his feeds were quickly increased from 10 to 85 mL/hr, which would provide approximately 70 kcal/kg/day; accounting for Casec supplementation, he would receive approximately 4 g/kg/day of protein. He developed some elements of the refeeding syndrome, including reductions in phosphorus, potassium, and magnesium levels, and return of diarrhea. He regained weight rapidly at an average of approximately 2.5 kg/week, probably reflecting not only body mass restoration but also fluid accumulation. Overall, however, his clinical condition improved -- he was able to be weaned off the ventilator, and he greatly regained strength in his extremities. However, shortly after transfer out of the ICU, he had sudden cardiorespiratory arrest (bradycardia to asystole and apnea) and could not be resuscitated. |
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