Effect of Liquid Pancreatic Enzymes on the Assimilation of Fat in Different Liquid Formula Diets

Written By: Sam Savage

Published Date: January 16, 2008 Last Edited: January 16, 2008

By Hauenschild, Annette Ewald, Nils; Klauke, Thorsten; Liebchen, Ariane; Bretzel, Reinhard Georg; Kloer, Hans-Ulrich; Hardt, Philip Daniel

ABSTRACT. Background: In some diseases, patients require high- calorie tube feeding with standard enteral formulas usually administered via temporal feeding tubes. One frequent pathophysiological condition in a relevant number of these patients is exocrine pancreatic insufficiency. Patients unable to swallow capsules might benefit from a liquid pancreatic enzyme (LPE) preparation. Methods: LPEs were prepared and mixed with different commercially available formula diets produced for enteral feeding. Lipolysis was then measured by fatty acid titration. Results: Complete lipolysis by liquid enzyme preparations was observed in diverse formula diets. Fat assimilation was even complete when LPE had been prepared 3.5 hours before the experiments, showing that the enzymes had been stable up to that time. Conclusions: The use of LPEs seems to be a good therapeutic option in patients with exocrine pancreatic insufficiency and the need for permanent high-calorie enteral feeding. Pharmaceutical companies should therefore be further encouraged to develop and distribute liquid enzyme preparations. (Journal of Parenteral and Enteral Nutrition 32:98- 100, 2008) The therapy of patients with short bowel syndrome, cystic fibrosis, several neurologic diseases, and acute and chronic pancreatitis, as well as the therapy of intensive care patients include high-calorie tube feeding with standard enteral formulas. These diets are usually administered via feeding tubes, specifically percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ).

However, a frequent pathophysiological condition that can be found in a number of these patients is exocrine pancreatic insufficiency, which leads to a relevant malassimilation of the fat contents in these diets. Especially in cystic fibrosis and chronic pancreatitis, exocrine insufficiency is a frequent finding, which is treated by pancreatic enzyme replacement therapy.1-3 Different forms of enzyme-containing drugs are currently commercially available. Yet all of them are packed in the form of capsules, which cannot be administered via feeding tubes. Therefore, the enzymes have to be swallowed, which can only be achieved in conscious and awake patients. However, some of the patients requiring enzyme replacement therapy are unable to swallow, and many of them even require continuous overnight feeding. These patients might benefit from a liquid pancreatic enzyme (LPE) preparation.

Several years ago, we reported the successful use of an LPE preparation for a patient with short bowel syndrome and exocrine pancreatic insufficiency.4 Thus, we investigated the assimilation of fat-containing standard liquid formula diets in vitro by LPE preparation.

MATERIALS AND METHODS

LPEs were prepared dissolving 1 g of pancreatin powder in 100 mL of 0.2% NaCl. The solution was then filtered through sterile gauze swabs (Fuhrmann GmbH, Much, Germany) to remove undissolved proteins. The pancreatin powder (Pankreon; Solvay Pharmaceuticals, Hannover, Germany) contained different amounts of lipase (312 U/g, 625 U/g, 1250 U/g, 2500 U/g, 5000 U/g). Then 2 mL of LPE were mixed with 10 mL of different commercially available formula diets produced for enteral feeding. Lipolysis was measured by fatty acid titration5: the pH was kept stable at pH 7 by neutralizing emerging fatty acids with NaOH titration. Lipolysis was calculated according to NaOH consumption (molar equivalent, mE) and fat content of the formula diets as declared by the manufacturers.

The following formulas were investigated (Table I):

* Fresubin Survimed OPD 2.4 g fat per 100 mL

* Fresubin Flussig 3.4 g fat per 100 mL

* Fresubin Supportan 7.2 g fat per 100 mL

* Fresubin Plussonde 3.4 g fat per 100 mL

* Pulmocare 9.2 g fat per 100 mL

* Nutricomp Immun 3.7 g fat per 100 mL

The experiments were performed at 37[degrees]C with or without the addition of bile acids (“Galle dispert”; KaliChemie Pharma GmbH, Hannover, Germany; 2 mL/2 minutes up to 16 mL) and with or without addition of calcium chloride (2 mol/L; 2 mL). Each titration experiment was performed for up to 20 minutes.

TABLE I

Fat content, protein:fat:carbohydrate relation, and manufacturer of the used formula diets

RESULTS

Pulmocare

Ten milliliters of Pulmocare containing 9.2 g of fat per 100 mL was used. For 100% lipolysis, 1.95 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. Complete lipolysis was observed using 5000 U, 2500 U, and 1250 U of lipase at different time points (Table II).

Pulmocare Using LPE After 3.5 Hours

Ten milliliters of Pulmocare containing 9.2 g of fat per 100 mL was used. For 100% lipolysis, 1.95 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. LPEs had been prepared 3.5 hours before the experiment using 5000 U of lipase. Complete lipolysis was observed after 5 minutes.

Fresubin Flussig

Ten milliliters of Fresubin Flussig containing 3.4 g of fat per 100 mL was used. For 100% lipolysis, 0.75 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. Complete lipolysis was observed in all LPEs but 312 U of lipase (Table II).

Fresubin Survimed

Ten milliliters of Fresubin Survimed containing 2.4 g of fat per 100 mL was used. For 100% lipolysis, 0.692 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. Complete lipolysis was observed in all LPEs used (Table II).

TABLE II

Lipolysis of fat in different formula diets using different amounts of lipase

Fresubin Supportan

Ten milliliters of Fresubin Suppotan containing 7.2 g of fat per 100 mL was used. For 100% lipolysis, 1.6 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. Complete lipolysis was observed using 5000 E and 2500 E of lipase (Table II).

Fresubin Plus Sonde

Ten milliliters of Fresubin plus Sonde containing 3.4 g of fat per 100 mL was used. For 100% lipolysis, 0.75 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. Complete lipolysis was observed in all LPEs used (Table II).

Nutricomp Immun

Ten milliliters of Nutricomp Immun containing 3.7 g of fat per 100 mL was used. For 100% lipolysis, 0.94 mE of NaOH was calculated to be needed. Sixteen milliliters of bile (15 mmol/L) and 2 mL of CaCl (2 mol/L) were added. Complete lipolysis was observed in all LPEs used except for 321 U of lipase (Table II).

DISCUSSION

Pancreatic enzyme replacement therapy is a well-accepted treatment that is necessary in a number of diseases accompanied by exocrine pancreatic insufficiency. To date, it has been well established in chronic pancreatitis and cystic fibrosis.1-3 However, it has been difficult to supply pancreatic enzymes with the formula diets in patients needing high-calorie enteral feeding because patients have to swallow the pancreatin preparations in the form of capsules. In many situations (eg, need of permanent continuous [24 hours] tube feeding or enteral nutrition via jejunal tube in pancreatitis), patients cannot therefore be supplied with adequate doses of enzymes.

Some time ago, we reported the successful use of an LPE preparation in a single case of short bowel syndrome in Crohn’s disease, with consequent exocrine insufficiency.4 Clinical results were promising. In order to investigate how long the enzymes are working and whether complete lipolysis of the fat contents in standard formula diets can be achieved, we performed the present in vitro experiments.

In this study, we could demonstrate complete lipolysis by liquid enzyme preparations in diverse formula diets. Fat assimilation was even complete when LPE had been prepared 3.5 hours before the experiments, showing that the enzymes were stable up to this time. Our experience using this technique in single patients suggests no adverse events or side effects.4 Thus, the use of LPE seems to be a good therapeutic option in patients with exocrine pancreatic insufficiency and need of permanent high-calorie enteral feeding.

Patients with severe acute pancreatitis are another subgroup of patients in definite need of high-calorie enteral feeding administered distal to the pancreas.6 Formula diets administered via jejunal feeding tubes, together with LPE solutions, could ensure high-calorie enteral feeding in this special group of patients.

Generally speaking, the suggested route of administration is jejunal feeding because intragastric administration might in all likelihood result in digestion of the used enzymes. According to our results, it seems reasonable to adjust the dosing of LPEs to the fat content and composition of the used formula diet. Concerning the timing of lipolysis, we recommend administration of the enzymes together with the formula diet as a freshly prepared premixed solution, yet a simultaneous administration of the formula diet and the LPE solution seems possible as well.

In the meantime, it has even become possible to prepare LPEs that are stable for several months (M. Galle, Solvay, oral communication, March 2006). Yet one must remember that long-term stability and sterility have not been adequately studied, and further research in this field is necessary to establish appropriate guidelines for LPE storage and use. Pharmaceutical companies are further encouraged to develop and distribute LPEs for use in this special group of patients.

ACKNOWLEDGMENTS

The authors thank Solvay Pharmaceuticals, Hannover, Germany, for providing the Pankreatin powder.

REFERENCES

1. Baker SS, Borowitz D, Duffy L, Fitzpatrick L, Gyamfi J, Baker RD. Pancreatic enzyme therapy and clinical outcomes in patients with cystic fibrosis. Pediatrics. 2005;146:189-193.

2. Anthony H, Collins CE, Davidson G, et al. Pancreatic enzyme replacement therapy in cystic fibrosis: Australien guidelines. Paediatr Child Health. 1999;35:125-129.

3. Layer P, Keller J, Lankisch P. Pancreatic enzyme replacement therapy. Curr Gastroenterol Rep. 2001;3:101-108.

4. Hardt PD, Helfrich C, Klauke T, Kloer HU. Liquid pancreatic enzyme therapy for a patient with short bowel syndrome and chronic pancreatitis in a complicated case of Crohn’s disease. Eur J Med Res. 1999;4:345-346.

5. Nilsson NO, Belfrage P. Continuous monitoring of free fatty acid release from adipocytes by pH-stat titration. J Lipid Res. 1979; 20:557-560.

6. Meier R, Ockenga J, Pertkiewicz M, et al. ESPEN guidelines on enteral nutrition: pancreas. Clin Nutr. 2006;25:275-284.

Annette Hauenschild, PhD; Nils Ewald, MD; Thorsten Klauke, MD; Ariane Liebchen, PhD; Reinhard Georg Bretzel, MD; Hans-Ulrich Kloer, MD; and Philip Daniel Hardt, MD

From the Third Medical Department, University Hospital Giessen und Marburg, Giessen, Germany

Received for publication April 3, 2007.

Accepted for publication June 15, 2007.

Correspondence: Nils Ewald, MD, Third Medical Department, University Hospital Giessen and Marburg, Giessen Site, Rodthohl 6, D- 35392 Giessen, Germany. Electronic mail may be sent to [email protected].

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