Mismanagement of high output stomas (HOS) can have a detrimental impact on the quality of life for patients. This article will discuss the pharmacological care and dietary management of HOS
The aims of treatment for HOS are:
- Prevention of thirst and dehydration
- Reduce stomal output to 1–2l/day depending on the patient’s current output or to manage diarrhoea
- Prevention of electrolyte deficiencies
- Increase absorption of fluids, nutrients, electrolytes and/or medications from the gastrointestinal tract.1–3
Managing fluid and magnesium loss
Patients with HOS are at risk of dehydration due to high fluid losses. This can lead to hypotension and potentially renal failure if not managed correctly. Monitoring for dehydration is important and patients are often asked if they feel thirsty or have a dry mouth. Accurate fluid balance monitoring charts, daily weights, serum creatinine, potassium, magnesium, and urine sodium are required to ensure patients are appropriately assessed for hydration.2 Management options vary on the degree of dehydration or stomal losses. Magnesium loss is also common in patients with high outputs potentially due to the absence of distal ileum and colon where most magnesium is absorbed.4 Medication such as proton pump inhibitors (PPIs) can also cause hypomagnesaemia and therefore checking patient’s medication list is important.
In the acute setting patients are often made nil by mouth to reduce stoma losses and intravenous fluids are given to re-hydrate. The type and volume of fluids prescribed is determined by the amount of fluid and electrolyte loss in a 24-hour period. Accurate fluid balance charts are important in helping medical teams decide the most appropriate fluids to prescribe. Table1 shows the average loss of electrolytes from different stomas to help guide in selection of fluids to prescribe.
Once stoma loss has been reduced, patients receive an oral hypotonic fluid (water, tea, coffee) allowance of up to 1l/day.6 While this sounds counter-intuitive for a patient who feels thirsty, hypotonic fluids containing <90mmol/l sodium cause a net loss of sodium and water into the bowel lumen.7 By reducing oral intake of hypotonic fluids and promoting drinking of solutions containing >90mmol/l sodium reduces loss and potentially increases absorption of sodium and water from the bowel. Our organisation (St Mark’s Hospital) has a formulation for an oral rehydration solution as detailed in Figure 1.
Glucose aids in sodium absorption in the bowel wall as uptake of sodium into cells is an active process.8 Double strength Dioralyte® (two sachets dissolved in 200ml of water or 10 sachets in 1l of water) is an alternative for those who find the St Mark’s solution less palatable. It is worth noting, however, that 10 sachets of Dioralyte® in 1l of water contains 40mmol potassium, which could present problems in patients in whom potassium intake should be restricted, for example, those with cardiac conditions. Patients are advised to chill the solution to make it more palatable. Drinking through a straw and sipping it through the day rather than trying to drink large amounts at a time often helps to complete the full litre. Patients can add a small amount of cordial to the solution to improve the taste; however, it is advised that this is a small amount so as not to offset the concentration of electrolytes.7
Hypomagnesaemia can cause muscle cramps and confusion.2 If patients are taking PPIs, it is sometimes worth considering switching these to a H2 receptor antagonist, which does not cause hypomagnesaemia. This is not always possible because PPIs are better at reducing gastric secretions than H2 receptor antagonists. In this case, the low magnesium can be managed by oral magnesium supplements. While these are easy to administer, they are not always the best option. Inorganic oral magnesium salts dissolve in fluid to create a hyperosmolar solution that promotes secretion of water into the lumen and thus increases stoma output.4 Organic magnesium salts are less likely to produce this effect and are therefore better tolerated. Magnesium aspartate is usually avoided. This comes as a powder and is dissolved in 50–200ml hypotonic solution for administration up to three times a day, and this would form part of the patient’s hypotonic fluid allowance.9 Magnesium supplements are given in doses of 12–24mmol/day and best taken at night when gut transit is slower as this allows for greater absorption.2 Where oral magnesium supplementation is not successful or worsens stomal output, long-term intravenous support might be considered; however, this is invasive and requires homecare services to be set up in the UK.
Antimotility drugs are used to reduce stomal output by slowing bowel transit time. This allows for increased contact time between the bowel and food thereby enhancing absorption of fluids and nutrients from the bowel.
The first drug of choice to reduce stoma output is loperamide. Loperamide is important in the management of colostomies or ileostomies, to reduce the volume of effluent and is preferred to opiate drugs (for example, codeine phosphate) as it is not sedative, addictive, and does not cause fat malabsorption.10 Loperamide is a synthetic opioid agonist, exerting its antimotility effects partly by stimulating mu opioid receptors on the circular and longitudinal muscle in the small bowel and may also reduce gastrointestinal secretions, resulting in a reduction in stoma output.10 Stimulation of the mu opioid receptors inhibits peristalsis of the bowel muscle thereby prolonging bowel transit time. In practice, counselling patients to take loperamide 30–60 minutes before food allows time for the medication to slow down peristalsis prior to the ingestion of food. The bowel therefore has more contact time with food and therefore increased absorption of nutrients and water.4
Loperamide passes through the enterohepatic circulation, which is severely disrupted in patients with a short bowel as small bowel transit may be very rapid. Thus, British Society of Gastroenterology guidelines on the management of patients with a high output jejunostomy or ileostomy suggest that high doses of loperamide above licensing (>16mg/day) may be needed.4
Several studies have investigated the benefits of loperamide. A double-blind, randomised, placebo-controlled study, consisting of a three-day treatment period with loperamide 12mg/day or placebo showed a reduction in ileostomy output and transit time with loperamide (p < 0.02).11 Additionally, a systematic review of pharmacotherapy for HOS identified five controlled studies with a total of 69 patients, all showing a reduction in output when loperamide was used at the licensed maximum dose of 16mg/day.12
It is important to note the MHRA drug safety alert issued in September 2017, which reports serious cardiac adverse reactions (QT prolongation, torsades de pointes and cardiac arrest) with high doses of loperamide.13 The British Intestinal Failure Alliance (BIFA) responded to the alert stating there were no reports of loperamide toxicity in patients with gastrointestinal diseases and, as loperamide absorption is likely to be much reduced in short bowel patients, doses of >16mg/day should continue to be used. BIFA recommended measuring loperamide serum levels where doses exceed 80mg/day.13 The risks of not treating a HOS in this cohort of patients are greater than the risks associated with high-dose loperamide.13
Codeine is another drug used off-label for its antimotility properties to reduce stoma output; it is a centrally acting weak opioid.14 Codeine stimulates mu opioid receptors and doses vary from 30–60mg, 3–4 times a day. The MHRA released a drug safety alert for the risk of potential fatal respiratory depression and the risk of dependence and addiction associated with codeine.14 Patients can metabolise codeine to varying degrees and a marked increase in morphine toxicity can be seen in patients who are ultra-rapid codeine metabolisers (CYP2D6 ultra-rapid metabolisers). Conversely
a reduced therapeutic effect can be seen in poor codeine metabolisers.14
There has been previous research showing a decrease in water and sodium output from an ileostomy with use of codeine and loperamide by approximately 20–30%.4 The synergistic effect of codeine and loperamide is known to be effective in controlling HOS, with high doses being required due to malabsorption in the bowel.8
PPIs are substituted benzimidazoles that are activated in the acidic environment of the parietal cells of the stomach lining. They irreversibly inhibit the H+K+ ATPase enzyme reducing basal and stimulated gastric acid secretion.15 PPIs reduce the volume of stomach acid produced by the parietal cells, and are therefore useful in patients with intestinal failure (IF) and HOS, as the result is reduced overall fluid loss with no effect on energy or micronutrient absorption.16,17 Their ability to reduce stoma output in patients with short bowel has been demonstrated in several double-blind, placebo-controlled studies.18,19
PPIs can be taken orally in patients who are able to sufficiently absorb, but for patients with <50cm of jejunum remaining, intravenous PPIs should be used. In patients with an ileostomy the administration of PPIs can effectively reduce output volumes as well as increasing the absorption of salts.19 Commonly used PPIs include omeprazole, lansoprazole and pantoprazole. Patients should be advised to take PPIs on an empty stomach approximately 30–60 minutes before food because they are only effective on active H+K+ pumps.20
H2 receptor antagonists such as ranitidine also reduce gastric secretions and are therefore effective at reducing stoma output. They can be considered when patients are experiencing hypomagnesaemia with PPIs. Ranitidine should be given at a dose of 300mg twice daily.
Somatostatin analogues such as octreotide and lanreotide can also be beneficial in the management of HOS patients with IF, by reducing intestinal output whilst maintaining micronutrient and energy absorption.21 Octreotide is a long-acting analogue of somatostatin which works by delaying gastric and small bowel emptying and reducing salivary, gastric and pancreaticobiliary secretions, while having no effect on energy or nitrogen absorption in patients with HOS. It is effective for use in high output ileostomies or jejunostomies. Octreotide should be started at a dose of 50 micrograms twice a day subcutaneously and titrated up to 100 micrograms three times a day depending on response and tolerability.7 One placebo-controlled double-blind crossover study found that octreotide significantly reduced fluid losses when compared with placebo (p<0.001) as well as reducing jejunostomy losses of sodium, potassium and chloride (p<0.001).22 Another double-blind, placebo-controlled balance study concluded that octreotide administration leads to a significant decrease in water and sodium losses via jejunostomies and ileostomies having no effect on the net absorption of calcium, magnesium, potassium, phosphate and zinc.23
The use of octreotide in IF patients can have disadvantages; the clinical response can be unpredictable; it increases the patient’s risk of developing cholethiasis; it has been suggested that it may affect intestinal adaptation post-surgery; postprandial hypoglycaemia has been reported; and injections can be unpleasant for patients.15,24 Furthermore, it has been suggested that macronutrient absorption may be impaired by somatostatin in patients with short bowel syndrome, by inhibiting glucose absorption and pancreatic enzyme secretion,4 hence, somatostatin analogues should be reserved for patients who have a resistant HOS.7 Longer-acting somatostatin analogues are available for use in patients who have trialled octreotide and in whom it is found to be effective. Lanreotide is an octapeptide analogue of natural somatostatin that has similar effects to octreotide but is administered subcutaneously every 28 days.
Clonidine is an alpha2-adrenergic receptor agonist which has been used off-label in patients with short bowel and HOS. Case studies have shown that it can effectively decrease intestinal fluid and electrolyte losses by inhibiting gastrointestinal motility and thereby increasing absorption of sodium and water in the bowel.25 The doses used in these case studies were 0.1–0.2mg orally twice daily. A single open-label study demonstrated an approximate 10% decrease in stomal wet weight in short bowel patients with a jejunostomy after the application of a 0.3mg transdermal patch, with no patients in the study developing hypotension.26
Patients with HOS have higher energy requirements due to the reduced absorption of nutrients. They need to ingest more calories in a day to get the most out of their intake. Patients are advised to eat a high fat and low fibre diet to ensure they can get high energy throughout the day.27 The longer food is in contact with the mucosa of the small bowel the higher the chance of absorption of nutrients. Low fibre foods (for example, white bread, rice or pasta) travel more slowly in the bowel and are therefore advised over high fibre foods (for example, wholemeal bread, rice or pasta).28
Patients are encouraged to snack frequently throughout the day between meals rather than having three large meals to keep outputs manageable and to ensure they can reach their target calorie intake during the day. They are also often advised to avoid drinking fluids just before or after meals to stop the food being flushed through by the fluid.28
Most fruits and vegetables are usually discouraged due to their high fibre content. While it has been shown that avoiding fibre helps to increase the patient’s calorie intake, it is also worth noting that patients can find it difficult to stick to the high calorie diet. It is important to work with them to find the right balance between the pleasure of eating fibrous foods and managing their output. Soft fruits, or those which can be mashed (such as bananas) are acceptable for some patients. Cooking vegetables well (root vegetables are better tolerated than green vegetables) and advising patients to chew their food well also helps to reduce the high outputs.28 Adding additional salt to food during cooking and at the time of eating increases the sodium content of the food and this, as discussed earlier, helps to reduce sodium and water loss via the stoma by increasing the sodium concentration within the lumen of the bowel.2
Much of the evidence behind diets for HOS patients is anecdotal and as such it is recommended that patients speak to specialist dietitians who would ensure advice given is tailored individually.4
Pharmacokinetics and stomas
Drug absorption mainly occurs in the upper small bowel, although it can also occur to a lesser extent throughout the gastrointestinal tract. This is due to the presence of villi structures in the small bowel that increase surface area, an optimal pH for drug absorption, and a high blood flow maintaining a concentration gradient to allow for absorption.29
The two major factors influencing oral drug absorption are drug solubility (drug solute dissolution in a solvent to give a homogenous system) and drug permeability (movement) across the bowel wall; the medication dose must disintegrate, dissolve, and maintain a concentration gradient within the intestinal fluid that is high enough to diffuse toward the gut epithelium and support drug absorption.30,31
The Biopharmaceutics Classification System, introduced in 1995, categorises drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics; this has been used to predict novel drug characteristics of the rate-limiting step in the intestinal absorption process following oral administration (Figure 2).
Bioavailability has an intrinsic effect on the rate and extent of drug absorption and therefore plasma drug concentration. There are several biological and physiologic GI barriers to oral drug absorption, and hence bioavailability, bowel lumen pH, enzymes, bile salts, transit time, mucus layer, villi, and epithelial cell membrane.
Following oral or enteral dosing of an immediate-release medication, bioavailability mainly depends on three processes; the percentage of absorbed dose, the first-pass extraction of the drug in the bowel wall and hepatic first-pass metabolism.32
What does this mean for stoma patients?
Knowledge of remaining bowel length is vital in determining how an oral drug dose is expected to be absorbed. Patients with a jejunostomy are less likely to absorb the full drug dose, compared with those with an ileostomy. Patients with >100cm of small bowel to an end jejunostomy are likely to absorb more of the drug dose compared with short bowel syndrome (SBS) patients (<100cm jejunum). Drug absorption is least affected in patients with colostomies, unless the medication is in a modified-release form, where the site of absorption is set out to be further along the GI tract.
Oral medication metabolism is likely to differ in patients of similar anatomies, as several factors play a role in determining outcome. If oral drug doses are seen whole in stoma content, alteration in formulation may prove beneficial in aiding absorption. Crushing tablets, opening capsules and dissolving the contents in water, and liquid formulations provide the same dose of drug in smaller particles. The decreased particle size and increased drug particle surface area increases the chance of absorption where the disintegration and/or dissolution processes have occurred outside the bowel. Pharmacists play a key role in ensuring that safe use of medication occurs when these processes are required.
Another point to consider is that even where a patient may appear to have a sufficient length of small bowel for drug absorption, the ‘quality’ of bowel function may be compromised; for example, in patients with Crohn’s disease, where there is a vast amount of inflammation and/or structuring, reducing surface area for absorption or preventing medication movement.29
Common mistakes to avoid in practice
To ensure appropriate management of short bowel, there are a few common mistakes frequently encountered in practice and which should be avoided.7
Mislabelling a jejunostomy as an ileostomy
It is important to distinguish the type of stoma a patient has so that proper diagnosis and early appropriate management can occur. Patients with a true ileostomy should not encounter the same problems associated with having a jejunostomy. Ileostomy patients might have a HOS during the immediate postoperative period but this usually settles. However, in patients with a jejunostomy, increased oral intake will significantly increase stoma output, and in these patients a short bowel regimen should be commenced.
Not recognising a high stoma output
When assessing stoma output it is important to consider it in proportion to the patients’ oral intake. A stoma output of 1.5l/day is not classified as high if the patient has an oral intake of 3l/day; however, it would be classified as high if the patient has an oral intake of only 500ml/day. It is also important to be aware that although HOS may be due to a short bowel there are other potential causes.
Dehydration can be excluded in SBS if the patient has normal urea and creatinine levels
Blood parameters of renal function can frequently be affected if the patient is sarcopenia and therefore has creatinine and urea concentrations below the normal range. Therefore, when the creatinine concentration is above the normal range this suggests significant renal impairment. To properly assess a patient for dehydration, a combination of parameters should be used, including any signs and symptoms of dehydration and laboratory test results.
Drinking more, in patients with short bowel, will lead to increased water absorption
In full intestinal anatomy, most of fluids and secretions are usually absorbed in the distal small bowel and colon, but due to the absence of the distal small bowel in these patients, they are in a permanent secretory state. The intake of hypotonic fluids results in a net secretion of sodium and water into the proximal small bowel lumen, thereby causing sodium and water depletion. Patients often experience significant thirst as a result of this depletion and it can be difficult for them to accept that increasing their oral fluid intake will only worsen their dehydration. This education is important and consistent information from the multidisciplinary team is key to helping patients manage their outputs.
Ignoring hypomagnesaemia and other mineral deficiencies
Patients with short bowel frequently experience mineral and vitamin deficiencies and therefore levels of zinc, selenium, and vitamin B12, as well as the fat-soluble vitamins should be checked regularly. It is usually advised to check these at six-monthly intervals but in patients where HOS are not well controlled, more frequent monitoring may be required.
Not having multidisciplinary approach to the management of HOS patients
This is extremely important when managing patients with HOS, as it is common for these patients to have a significantly reduced quality of life due to the combined physical and psychological aspects of their condition. Early input and advice from stoma nurses, specialist dietitians and specialist pharmacists is recommended to ensure patients are provided with the appropriate advice at an early stage. Early psychological and psychiatric intervention is also recommended due to the commonly associated anxiety and depression that arises following complex bowel surgeries and the resulting short bowel syndrome, which may never be reversed.
Overall, HOS management can require multiple interventions that work by different methods on the gastrointestinal tract. Many of the treatments are used off-license and therefore close monitoring and understanding of the treatments is important by the medical team. Understanding the patient anatomy and the type of stoma a patient has is crucial in determining the type of treatment required. Ultimately treatment should involve a multi-disciplinary approach to ensure that the patient achieves the best possible outcome.
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- Nightingale J, Woodward JM. Guidelines for management of patients with a short bowel. Gut 2006;55(suppl 4):iv1–2.
- Burch J. Back to basics: how to care for different types of stoma. Nurs Residential Care 2013;15(10):662–5.
- Pironi L et al. ESPEN guidelines on chronic intestinal failure in adults. Clinical nutrition. 2016 Apr 1;35(2):247–307.
- Padhi S et al. Intravenous fluid therapy for adults in hospital: summary of NICE guidance. BMJ 2013;347.
- Baker ML, Williams RN, Nightingale JM. Causes and management of a high-output stoma. Colorectal Dis 2011;13(2):191–7.
- Oke SM, Nightingale JM, Gabe SM. Mistakes in short bowel and how to avoid them. UEG Educ 2018:7–11.
- Smith L, Boland L. High output stomas: ensuring safe discharge from hospital to home. Br J Nurs 2013;22(5):S14–8.
- Magnaspartate 243mg powder for Oral Solution – Summary of Product Characteristics (SPC). www.medicines.org.uk/emc/product/1889 (accessed May 2021).
- Loperamide 2mg Hard Capsules (PL29831/0381) – Summary of Product Characteristics (SPC). www.medicines.org.uk/emc/product/1207/smpc#gref (accessed May 2021).
- Kristensen K, Qvist N. The acute effect of loperamide on ileostomy output: a randomized, double-blinded, placebo-controlled, crossover study. Basic Clin Pharmacol Toxicol 2017;121(6):493–8.
- de Vries FE et al. Systematic review: pharmacotherapy for high-output enterostomies or enteral fistulas. Aliment Pharmacol Ther 2017;46(3):266–73.
- Nightingale J, Meade U. British Intestinal Failure Alliance (BIFA) Position Statement The use of high dose loperamide in patients with intestinal failure. www.bapen.org.uk/pdfs/bifa/position-statements/use-of-loperamide-in-patients-with-intestinal-failure.pdf (accessed May 2021).
- Codeine Phosphate 30mg tablets – Summary of Product Characteristics (SPC). www.medicines.org.uk/emc/product/2375/smpc#gref (accessed May 2021).
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- Nightingale JM et al. Effect of omeprazole on intestinal output in the short bowel syndrome. Aliment Pharmacol Ther 1991;5(4):405–12.
- Aly A et al. Effect of an H2 receptor blocking agent on diarrhoeas after extensive small bowel resection in Crohn’s disease. Acta Med Scandinavica 1980;207:119–22.
- Jeppesen PB et al. Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection. Gut 1998;43(6):763–9.
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- Nightingale JM et al. Octreotide (a somatostatin analogue) improves the quality of life in some patients with a short intestine. Aliment Pharmacol Ther 1989;3(4):367–73.
- Lémann M et al. Effect of octreotide on fluid and electrolyte losses, nutrient absorption and transit in short bowel syndrome. Eur J Gastroenterol Hepatol 1993;5(10):817–22.
- Ladefoged K et al. Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome. Gut 1989;30(7):943–9.
- Farthing MJ. Octreotide in dumping and short bowel syndromes. Digestion 1993;54(Suppl 1):47–52.
- McDoniel K et al. Use of clonidine to decrease intestinal fluid losses in patients with high output short bowel syndrome. J Parenter Enteral Nutr 2004;28(4):265–8.
- Buchman AL et al. Clonidine reduces diarrhea and sodium loss in patients with proximal jejunostomy: a controlled study. J Parenter Enteral Nutr 2006;30(6):487–91.
- Baker M, Greening L. Practical management to reduce and treat complications of high-output stomas. Gastrointestinal Nurs 2009;7(6):10–17.
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