Review
Copyright ©The Author(s) 2021.
World J Gastroenterol. Jun 28, 2021; 27(24): 3440-3465
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3440
Table 1 Pathophysiological classification of intestinal failure (adapted from Pironi et al[2], 2015)
Type
Primary cause
Underlying disease
Short bowel typeQuantitative/qualitative loss of resorptive surfacePost-operative, in patients with mesenteric infarction, Crohn’s disease, radiation enteritis, familial polyposis, abdominal traumata, necrotizing enterocolitis1, bariatric obesity surgery (biliopancreatic diversion with or without duodenal switch), gastroileal anastomosis, extensive tumor resection.
Congenital, in patients with gastroschisis1, intestinal atresia1, intestinal malformation, omphalocele
Fistula typeBypass of resorptive surface due to jejunocolic fistulaInflammatory bowel disease (Crohn’s disease2, diverticulitis, radiation enteritis)
Post-operative3 in patients with neoplasia (colorectal carcinoma, ovarian carcinoma, Crohn’s disease)
Iatrogenic (post-op, percutaneous drainage)
Traumata
Foreign bodies
Dysmotility typeRestricted (insufficient) nutrition intake due to postprandial exacerbation of symptoms, to the point of non-mechanic ileus in severe casesOgilvie syndrome (acute non-mechanic obstruction of the colon)
Chronic intestinal pseudo-obstruction: Primary/idiopathic (neuropathic/myopathic); Secondary (collagenous vascular disease, e.g., PSS, LE, Ehlers-Danlos syndrome; neurological disorders such as Morbus Parkinson, intestinal hypoganglionosis; endocrinopathies)
Obstruction typeReduced nutrition intake; Increased secretion of liquid and electrolytes in obstructive segments of the intestine; Loss of liquids and nutrients due to recurrent vomiting and/or "overflow sensors""Frozen abdomen" in patients with peritoneal carcinomatosis, extensive intestinal adhesion, recurrent peritonitis.
Neoplastic stenoses and/or strictures
Incarceration/strangulation of the intestine (hernia)
Volvulus
Mucosa typeExtensive loss or damage of mucosa results in insufficient resorption of nutrients and pronounced enteral lossMicrovillus inclusion disease1
Tufting enteropathy (intestinal epithelial dysplasia)
Tricho-hepato-enteric syndrome
Autoimmune enteropathy
Intestinal lymphangiectasia
Protein-losing enteropathy (Morbus Waldman)
Radiation enteritis
Chemotherapy-induced/associated enteritis
Table 2 Recommended laboratory monitoring for patients receiving parenteral nutrition (adapted from Lappas et al[29], 2018)
ParameterFrequency
Initiation of therapy (acute care)
Long-term therapy
Capillary glucoseEvery 6 h until advanced to goal and as needed to maintain 140-180 mg/dLNot routine, as needed basis to coordinate with PN infusion cycle
Basic metabolic panel Phosphorus, magnesiumDaily, until advanced to goal and stable; then 1-2 times/wkWeekly, then decrease frequency as stable
CBC (with differential)Baseline; then 1-2 times/wkMonthly, then decrease frequency as stable
Liver function: ALT, AST, ALP, total bilirubinBaseline; then weeklyMonthly, then decrease frequency as stable
Serum triglyceridesBaseline if at risk; then as neededNot routine, as needed
Iron studies, 25-OH vitamin DNot routine (see Table 4)Baseline, then every 3-6 mo
Zinc, copper, selenium, manganeseNot routine (see Table 4)Baseline, then every 6 mo
Table 3 Nutrition therapy (macronutrients) according to presence or absence of colon (modified from Pironi et al[46], 2016)
Nutrient
Colon present (partial/complete)
Colon removed or disabled
Carbo-hydratesSlow increase of the proportion of complex carbohydrates up to approx. 40%-50% of total calorie intake, no low molecular weight sugarsSlowly increase the proportion of complex carbohydrates up to approx. 40%-50% of total calorie intake, no low molecular weight sugars, modified FODMAP diet
ProteinUp to 20%-30% of total energy intakeProtein: up to 20%-30% of total energy intake
FatUp to 20%-30% of total energy intakeFat: up to 40% of total energy intake
Ensure adequate essential fatty acids (high EFA content)Ensure adequate essential fatty acids (high EFA content)
Consider MCTsLimit MCTs
FiberDietary fiber supplements: up to 5-10 g/dDietary fiber supplements: up to 5-10 g/d
OxalateDiet low in oxalic acid and fats; Replacement of up to 50%-75% of dietary fat with MCTsNo restriction of oxalic acid necessary
FluidsEven if liquids are well tolerated, iso- and hypotonic drinks are preferableOral rehydration solutions frequently required
Lactose Low lactose diet (10-12 g)Unrestricted lactose intake
Table 4 Symptoms, prophylactic supplementation, and therapy of frequent (critical) nutrient deficiencies in chronic intestinal failure
Nutrient
Symptoms of deficiency
Normal values (blood/serum)
Additional lab tests
Prophylaxis
Therapy in case of deficiency
CalciumNeuromuscular hyperarousal, cardiovascular symptoms, osteopathy2.1-2.7 mmol/L↑Alkaline phosphatase; ↑intact PTH; ↓Bone mineral density Calcium citrate, oral 1200–2000 mg/dBisphosphonate if T-Score < 2.5
MagnesiumNeuromuscular hyperarousal, osteopathy (PTH effect ↓) 0.75-1.15 mmol/L↓Magnesium in urineMagnesium citrate, oral 300 mg/d10 – 15 mmol magnesium, e.g., in 1000 mL NaCl 0.9 %
Vitamin ANight blindness, wound healing disorders1.05-2.80 µmol/L↓Plasma retinol; ↓Retinol binding protein10000-50000 U/d, if liver function normalNo corneal changes: 10000–25000 IU/d oral for 1–2 wk; Corneal changes: 50000–100000 IU i.m. followed by 50000 IU/d i.m. for 2 wk
Vitamin DOsteopathy, wound healing disorders, immune system disorders< 20 µg/L: deficiency; 20-30 g/L: insufficiency; > 30 µg/L: sufficient supplies↑Alkaline phosphatase; ↑intact PTH; ↓Bone mineral density Oral vitamin D (400–800 U/d) [ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3)] or 100000 U/3–6 mo orally50000–150000 IU oral 3-5 times a week; If required: calcitriol [1,25(OH)2D] oral
Vitamin KHemorrhagic diathesisINR < 1.2PIVKA 10 mg/wkN/A
Vitamin B1Polyneuritis (“dry form“), edema, tachycardia, Cardiac insufficiency (“wet form“); Wernicke encephalopathy, ataxia (“central form“)10.64 µg/L↓Thiamine pyrophosphate; ↓Erythrocyte transketolase activityIf vomiting, aggressive oral thiamine supplementation with 100 mg/d for 7–14 dTreatment of Wernicke Encephalopathy: 500 mg i.v. 3 ×/d for 2-3 d; ≥ 250 mg/d i.v. for 5 d; 30 mg oral 2 ×/d
Vitamin B12Megaloblastic anemia, glossitis, skin and mucous membrane pallor, paresthesia, polyneuropathy, funicular myelosis156-675 pmol/L↓Holo-TC; ↓MMA; ↑HomocysteineOral: 1000 μg/wk or 250–350 μg/d, i.m./s.c.: 1000 μg/mo or 3000 μg every 6 mo1000 or 2000 μg/d oral or 1000 μg/wk i.m.
ZincWound healing disorders, hair loss, taste disturbances, predisposition to infection 11-23 mol/L↓Zinc in urineIn presence of fistula, diarrhea or stomata: 12 mg; Otherwise: 3-4 mg30-45 mg (as zinc histidine), 220-440 mg (as zinc sulphate). For each 8–15 mg of elementary zinc, 1 mg copper should be substituted
IronAnemia, hair loss, cognitive disorders, predisposition to infectionCRP < 5 µg/L: > 30 µg/L; CRP ≥ 5 µg/L: ≥ 100 g/L↓Transferrin saturation; ↑Soluble transferrin receptor; ↑Zinc protoporphyrinOral max: 100–150 mg ironParenteral, depending on iron status: Aim: normalization of Hb plus transferrin saturation 35%-50% (calculated according to Ganzoni)
CopperNeutropenia, iron deficiency anemia, central venous development disorders11-22 µmol/L↓Copper/zinc superoxide dismutaseCopper gluconate, oxide or sulphate equivalent to 2 mg elementary copper; 1 mg copper for each 8-15 mg zincCopper sulphate equivalent to 2.4 mg elementary copper in 100 ml 0.9% NaCl i.v. administered one hour/d for 5 d. Subsequently, oral substitution as required
Table 5 Symptomatic treatment options in short bowel syndrome
Symptom
Drug/therapy
Dose (per day)
Gastral hypersecretionProton pump inhibitors20-40 mg i.v. (p.o.)
Clonidine2 × 75-150 µg s.c./p.o.
Octreotide (sandostatin)13-4 × 50-100 µg s.c.
HypermotilityLoperamide4-6 mg p.o. (max daily dose 16 mg)
Diphenoxylate4 × 2.5-7.5 mg (max daily dose 20-25 mg)
Codeine30 mg p.o.
Opium tincture4 × 0.3-1 mL (10-60 mg) p.o.
Secretory diarrheaOctreotide (sandostatin)12-3 × 50-100 µg s.c.
Budesonide (e.g., entocort)3 × 3 mg p.o.
Clonidine2 × 75-150 µg s.c.
Fat malabsorptionPancrelipase (e.g., Creon)40000 IU with main meals (15000 IU with snacks)
Lactose malabsorptionLactase formulations (L-products)Depending on severity
Reduced fluid resorptionLocust/carob bean gum flour added to drinks (yoghurt)Approx. ½-1 tablespoon per glass/pot
Kaopectate (kaolin/pectin)4 × 1 tablespoon
Table 6 Major complications of short bowel syndrome: risk factors, prevention and treatment (adapted from Pironi et al[46], 2016)

Risk factors
Prevention and/or treatment
Bacterial overgrowth/ miscolonizationIleocecal valve resection; Reduced intestinal motility (Ogilvie syndrome; chronic intestinal pseudo-obstruction)Metronidazole (500 mg, 2 times per day), vancomycin (125 mg, 4 times per day), neomycin (500 mg, 3 times per day), clindamycin (300 mg, 3 times per day) tetracycline (500 mg, 3 times per day), rifaximin (550 mg, 2 times per day)
Renal failureDehydration; CRBSI; Nephrocalcinosis; Kidney stonesOptimize fluid and sodium balance; Optimize CVC care; Prevent urinary calcium oxalate formation
Calcium oxalate, kidney stonesSBS with colon in continuity and fat malabsorption (enteric hyperoxaluria); Pyridoxine or thiamine deficiency; Excess of ascorbic acid; Dehydration; Low urinary citrate; Low urinary magnesiumReduce or avoid excess lipid in the diet; Reduce food with high oxalate content; Oral calcium at mealtime (1 g); Oral cholestyramine; Optimize fluid balance; Optimize acid-base balance; Optimize magnesium status; Limit ascorbic acid supplementation
BAMS
—CompensatedExtent of resection < 100 cm; Fecal bile acid excretion increased; Adequate hepatic compensation of bile acid loss; ≥ reduction of bile acid pool; no or minimal steatorrheaColestyramine/Colesevelam
—DecompensatedExtent of resection > 100 cm, fecal bile acid excretion increased; Inadequate hepatic compensation of bile acid loss; ≥ reduction of bile acid pool ≥ steatorrheaFat-modified/-reduced diet; Cholylsarcosine/ox gall1
GallstonesProlonged oral fasting; Interrupted bile acid entero-hepatic circulation; Prolonged treatment with anticholinergic and narcotic drugsLimit periods of oral fasting; Limit narcotic or anticholinergic treatment; Use oral and/or enteral feeding as much as possible
IFALD-cholestasisSBS with < 50 cm of residual small bowel; SBS without colon; CRBSI episodes; Chronic intraabdominal inflammation and/or small bowel bacterial overgrowth; Interrupted enterohepatic circulation of bile acid; Oral fasting; PN-overfeeding; i.v. soya-based lipid emulsion ≥ 1 g/kg/dAvoid oral fasting; Optimize CVC care; Treat intraabdominal inflammation foci; Rehabilitative surgical procedures; Optimize i.v. feeding; i.v. soya-based lipid emulsion < 1 g/kg/d and/or i.v. fish oil lipid emulsion
D-lactic acid acidosisSBS with a colon in continuity; Carbohydrate and soluble fiber-based diet; Ingestion of rapidly fermentable simple sugars; Feeding D-lactate containing food; High blood and urinary oxalate; Thiamine deficiency; Antibiotic and/or probiotic courses; Dehydration; Decreased renal function; Decreased liver functionLow carbohydrate and simple sugar diet; Antibiotics active against D-lactate-producing bacteria orally, such as metronidazole (500 mg, 2 times per day), vancomycin (125 mg, 4 times per day), neomycin (500 mg, 3 times per day), clindamycin (300 mg, 3 times per day), tetracycline (500 mg, 3 times per day), rifaximin (550 mg, 2 times a day); Thiamine supplementation; Reduction of oxalate absorption; Optimize fluid balance
Table 7 Pathophysiological characteristics of short bowel syndrome with and without colon in continuity (adapted from Pironi et al[46], 2016)
Characteristic
End-jejunostomy
Jejunocolic or jejunoileal anastomosis
Structural and functional adaptation, to increase nutrient absorptionNo evidence thereof at any time after surgeryPossible up to 2 yr after surgery
Gastric hypersecretion (up to 6 mo after resection)PresentPresent
Gastric emptying and small bowel transitAccelerated gastric emptying for liquidsSlowed
Accelerated small bowel transit
GI hormone secretion (PYY, GLP-1, GLP-2)Decreased/absentIncreased
Energy absorption from microbiota SCFA, production in the colonAbsentIncreased up to 1000 kcal (4.2 MJ) per day
Water and sodium absorption in the remnant small bowelPossible “net secretion” when jejunum length < 100 cm (more fluid and sodium lost than ingested)Colon adaptation can increase the absorption of water up to 6 liters and sodium up to 800 mmol per day
Vitamin B12 and bile salt absorptionAbsentPartially conserved or absent
Magnesium absorptionDecreasedDecreased
Remnant small bowel cut-off length for HPN weaning> 115 cmJejunocolic anastomosis > 60 cm
Jejunoileal anastomosis with ICV and entire colon
> 35 cm
Table 8 Intestinal failure-associated liver disease risk factors in adult patients with home-based parenteral nutrition (adapted from Van Gossum et al[157], 2019)
PN-related
Patient-related
Energy overfeedingLack of oral feeding
Glucose overload > 7 mg/kg/minShort bowel syndrome (small bowel remnant < 50 cm)
Lipid emulsion overloadInflammation/infection
Soya-based lipid emulsion > 1 g/kg/dSepsis (e.g., central venous catheter related)
Continuous infusion (24/24 h)Small intestinal bacterial overgrowth
Contaminants (phytosterols)Gut inflammation
Antioxidant deficiencyViral infection (e.g., hepatitis B, C)
Nutrient deficiency (choline, carnitine, methionine, taurine, essential fatty acid deficiency, etc.)Autoimmune
Hepatotoxic medications