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Newsletters: Managing Complications in HPN Consumers (Part II)
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Managing Complications in HPN Consumers (Part II)

Lyn Howard, MB, FRCP, FACP, Albany Medical Center

The following overview of HPN complications is excerpted from Gastroenterology, Volume 124, “Management of Complications...” by Howard, et. al., pages 1651-1661, © 2003 with permission from the American Gastroenterological Association. Last issue we covered the infectious and mechanical complications; this issue we will conclude with metabolic complications. The original article contains additional background information as well as sections on psycho-social issues and referral to an intestinal failure center, and is available from www2.gastrojournal.org.


Metabolic Complications

Fluid and Electrolytes.

This is a critical issue for short bowel patients. Many patients after a period of adaptation can absorb enough oral calories and protein to maintain their weight, often by eating four to six thousand calories/day. But using the gut can induce large enteric (bowel fluid) losses especially in the individual with a high jejunostomy. Such a patient may loose 4 L/day compared to a stool loss of 100 ml/day in a healthy person. Large enteric fluid losses can be exacerbated by a number of factors (Table 2) and sipping oral rehydration solutions may help address some of these losses, but usually parenteral hydration is required. This hydration fluid should be enough to produce a urine output of > 1 litre/day.

A number of reports have pointed to slow deterioration of renal (kidney) function in long term HPN patients. This may reflect the impact of nephrocalcinosis (kidney stones) from excessive oxalate absorption in patients with an incontinuity (surgically connected) colon or the intermittent use of antibiotics that are toxic to the kidneys, however chronic dehydration may well be an important common denominator. Excessive oxalate absorption in the colon and hyperoxalouria (excessive oxalate in urine) are a consequence of severe steatorrhea (loss of unabsorbed fat in stool). Recent studies show that conjugated bovine bile salts improve fat absorption and reduce urinary oxalate, but at the cost of more diarrhea. Cholylsarcosine, a synthetic bile salt analogue not broken down by bowel bacteria, has a more modest effect on fat and oxalate absorption but causes less stool output. In addition to renal problems, chronic dehydration causes fatigue and even low grade fever, late in the day before the cycled infusion is restarted.

To help short bowel HPN patients understand the precariousness of their fluid balance, it is useful to start out with the patient keeping careful input/output records. This is also important when the patient is starting to wean off HPN. Providing extra hydration fluids at home is useful so patients can boost their parenteral fluid intake on a hot day or after a dietary indiscretion. Hydration fluid can provide not only sodium, potassium, chloride and bicarbonate equivalents (actate/lactate) but also divalent cations, vitamins and trace elements for the patient who has weaned off full parenteral nutrition.

Several micronutrient deficiencies were described in the early years of long term parenteral nutrition patients, notably essential fatty acid, vitamin A, vitamin E, thiamin, biotin, zinc, copper, chromium, selenium and molybdenum. Over the past 30 years the commercial parenteral lipid, multivitamin and trace element preparations have added or increased these micronutrients so deficiency syndromes of these micronutrients are now rare. If they do occur, it is when patients are weaned off HPN to full dependence on oral nutrition. Iron deficiency may occur because it is not routinely added to parenteral solutions and many patients have ongoing disease-related enteric blood loss or frequent blood test monitoring. Routine blood testing should be limited in stable long term patients to perhaps 3 or 4 times/year.

There have been recent reports of excess manganese accumulating in the brain of HPN patients, presenting with Parkinsonian – like symptoms. Manganese, like copper, is excreted in bile, but can accumulate, especially in the presence of liver disease. Following reduction of manganese intake, abnormal MRI signals slowly disappear over a 3 year period. Parenteral vitamin D in doses originally supplied in the multivitamin formulation (400 IU/day) appear to increase bone resorption rather than support bone formation. Parenteral formulations now provide decreased vitamin D (200 IU/day).

Liver dysfunction: Mildly abnormal liver function tests (elevated alkaline phosphatase, transaminases >1.5 time normal upper limits) are common in HPN patients. This may reflect hepatic (liver) dysfunction due to pre-existing illness, for example Crohn’s disease or toxic hepatitis secondary to intra-abdominal infection, or some dysfunction precipitated by parenteral nutrition, developing after a few months on therapy. Liver biopsies usually show pericholangitis (inflammation around the bile ducts) and bile duct plugging. In most patients these abnormalities remain stable but in a few, more serious hepatic dysfunction develops and biopsies show extensive fibrosis with bridging, going on to cirrhosis. A recent study in France reported 22% of deaths in long term HPN patients were due to liver failure. In the US, liver disease accounts for 15% of HPN deaths in long term patients. Liver disease is more common in very short bowel patients (remanent <50 cms) and in children. The French study found a strong association between liver disease and a parenteral lipid intake of > 1 g/kg/day. One possible explanation for a lipid toxic effect is the presence of phytosterols (plant cholesterol) in lipid solutions. Different lipid solutions appear to have different toxicity even when the basic ingredients of soy oil and egg phospholipid are the same.

Many factors other than just parenteral lipid, are thought to contribute to HPN liver disease. Current research is particularly focused on hepatic transulfuration pathways (shifting of sulphur from one important biological compound to another in the liver). Methionine is the only sulphur containing amino acid in most parenteral formulations, because other sulphur containing amino acids are relatively insoluble and difficult to incorporate. However, methionine delivered systemically (e.g. via HPN), rather than via the normal, physiologic portal route, results in a shortage of critical sulphurated byproducts. HPN patients and animal models have demonstrated depleted choline, lecithin, carnitine, cysteine, glutathione and taurine levels. All these sulphur containing products have important functions in mobilizing fat and synthesizing lipid membranes with receptor and transport functions for the secretion of bile pigment.

Table 3 lists approaches with some evidence of benefit in managing HPN cholestasis. If liver damage continues and biopsies show bridging or early cirrhosis, the patient should be listed for small bowel/liver transplantation. In patients with fatal outcome the interval between onset of jaundice and death was 10 months.

Overlapping the problem of cholestasis (impaired excretion of bile pigment) is bile sludge and cholelithiasis (gallstones). About 25% of short bowel patients develop gall stones and require cholecystectomy (gallbladder removal). Prophylactic cholecystectomy at the time of the initial surgery is probably not warranted if the gall bladder is healthy at that point. Oral intake of some fat and ursodeoxycholate therapy reduces the risk of cholelithiasis.

Bone disease in HPN, like liver complications is present in a high percentage of patients in a mild form and presents as a major problem in a few. Cross sectional studies of bone mineral density using dual energy x-ray absorptionmetry (DEXA scan) showed a T score below -1 in 84% of 165 HPN patients and T Score below -2.5 in 41%. The lower T scores were associated with bone pain in 35% of patients and with a pathological fracture in 10%. Multiple factors that can contribute to bone disease including malabsorption syndromes, pre-existing liver disease, steroid administration, high levels of cytokines and other factors. Much of the problem relates to the primary disease and its treatment, and predates HPN.

Bone turnover studies in HPN patients show a low rate of bone formation with low serum osteocalcin. In the early years of HPN, aluminum contamination was a serious problem but this largely stopped when synthetic amino acid solutions replaced hydrolysates. Some batches of parenteral additives, such as calcium gluconate, are still contaminated and the Food and Drug Administration (FDA) is studying ways to eliminate this problem. Removal of vitamin D is recommended if the parathormone and hydroxy vitamin D levels are low. Amino acids result in hypercalcuria (too much calcium in urine), so reducing protein to <1.5g/kg/day is appropriate.

Low magnesium is common in short bowel patients. Magnesium is critical in gut absorption of calcium and magnesium. It is also important in activating parathormone and renal conservation of calcium. Magnesium status is best measured by a 24 hour urine collection. Less than 50 mg of urinary magnesium/day suggests magnesium depletion. An HPN formula for a short bowel patient, with normal renal function, should provide 20-25 meq Mg/day. Oral calcium supplements of 1-2 g/day are probably safer than large doses of calcium in the parenteral formula. There has been a serious problem of calcium phosphate crystals causing microvascular pulmonary emboli, fatal in two patients. This led to an alert by the FDA. Studies subsequently showed the importance during HPN solution preparation of modestly reducing the high pH of the amino acid solutions, adding most of the water early, agitating constantly throughout the mixing process and adding calcium last.

Bisphosphonates decrease bone resorption. Given cyclically, intravenous clodronate stabilized but did not increase spinal bone density over a 12 month period in 20 HPN patients. Calcitonin given intravenously for ten days relieved the bone pain in a severely demineralized patient. It is not clear if calcitonin has a long term role in treatment of HPN bone disease.

In summary, much progress had been made in the management of HPN complications since the first patient was sent home on this therapy in the late 1960’s. Proper training of HPN patients and caregivers, as well as careful management by experienced clinicians can further minimize the risks from therapy complications.


Table 2: Managing Excessive Enteric Loss in Short Bowel Patients


1. Constant thirst, excessive drinking of water, despite objective evidence of adequate hydration

2. Hyperosmolar food and fluid sources

3. High gastrin levels as patient adjusts to HPN, usually first 6 months but may be longer if ostomy output remains acid

4. Dysmotile segment, bacterial overgrowth, worsening of absorption and aggravation of gall stones. Stricture of bowel or at ostomy, proximal dilation and stimulated secretion


1. Possible thirst mechanism is dry mouth from anticholinergics (such as lomotil and imodium) or rapid upper bowel decompression so baroreceptors in duodenum do not signal adequate hydration. Patient has to learn to resist stimulus to drink excessively and to sip oral rehydration solutions so fluid and electrolyte losses are less critical .

2. Patient should limit foods or drink with high sugar content (such as soda) or nonabsorbable sweeteners (xylitol, sorbitol).

3. Treatment is parenteral H2 blockers. This blocks acid production while permitting the stimulus gastrin provides the proximal small bowel.

4. Trial of antibiotics to suppress growth of abnormal flora and probiotics to promote growth of normal flora. A longitudinal intestinal lengthening and tapering procedure should be considered.

Radiologic confirmation. Endoscopy and biopsy to establish cause. Balloon dilatation, stricturoplasty or surgical revision as needed.


Table 3: Medical Management of HPN Cholestasis

Some evidence of benefit

1. Encourage oral intake, or if necessary start enteral feedings

2. Limit parenteral calories glucose/lipid to modest amounts

3. Treatment of bacterial overgrowth syndromes with cycled antibiotics/probiotics and prokinetics

4. Oral lecithin, oral choline; or parenteral carnitine

5. Ursodeoxycholic acid 20-30 mg/kg/day


1. Stimulates bile output.

2. May provide critical nutrients

3. Excessive intake of all types of parenteral calories aggravates steatosis

May require surgical reconstruction of dilated non-motile segment.

4. Parenteral choline under investigation

5. May increase diarrhea

This website is an educational resource. It is not intended to provide medical advice or recommend a course of treatment. You should discuss all issues, ideas, suggestions, etc. with your clinician prior to use. Clinicians in a relevant field have reviewed the medical information; however, the Oley Foundation does not guarantee the accuracy of the information presented, and is not liable if information is incorrect or incomplete. If you have questions please contact Oley staff.


Updated in 2015 with a generous grant from Shire, Inc. 


This website was updated in 2015 with a generous grant from Shire, Inc. This website is an educational resource. It is not intended to provide medical advice or recommend a course of treatment. You should discuss all issues, ideas, suggestions, etc. with your clinician prior to use. Clinicians in a relevant field have reviewed the medical information; however, the Oley Foundation does not guarantee the accuracy of the information presented, and is not liable if information is incorrect or incomplete. If you have questions please contact Oley staff.
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