Viscosity Thickened Enteral Formula

Diet and Nutrition in Critical Care DOI 10.1007/978-1-4614-8503-2_27-1 # Springer Science+Business Media New York 2014

Viscosity Thickened Enteral Formula Satomi Ichimarua* and Teruyoshi Amagaib a Department of Nutrition Management, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan b Department of Food Science and Nutrition, School of Human Environmental Sciences, Mukogawa Women’s University, Nishinomiya, Japan

Abstract Thickened enteral formula (TEF) is a formula in which viscosity is intentionally increased by adding thickener to prevent enteral nutrition-related complications, such as diarrhea, nausea, vomiting, and gastroesophageal reflux (GER). Three types of TEFs are available at present: intragastric TEF, TEF prepared by mixing liquid enteral formula and thickener, and ready-to-use type. The positive effects of TEF are considered to be based on its high viscosity, which reduces the outflow rate of gastric contents and thereby helps to prevent diarrhea and GER. While several studies have been conducted on TEF with viscosity ranging from 900 to 20,000 mPa s, the mechanisms of TEF have not been fully demonstrated. TEF efficacy with regard to reducing complications of EN should not be determined based solely on quantitative viscosity data, as modalities for measuring viscosity and assessing complications subsequent to administration have not been standardized. Potential advantages of TEF include prevention of GER, diarrhea, skin trouble around the percutaneous endoscopic gastrostomy puncture site, and improvement of blood glucose levels and quality of life for both patients and caregivers. However, most previous studies of TEF have been empirical in nature, with little scientific evidence available supporting the efficacy of TEF in preventing complications of EN. TEF administration is only successful when functions of gastric motility, enterokinesis, digestion, and absorption are all normal. When applying TEF, bacterial contamination, feeding tube shape, timing and volume of administered water, and nutrient interactions should be considered. Given the present findings, TEF appears more suitable for use in patients in long-term care hospitals, nursing homes, or home medical care settings than acute care hospitals. Establishing a solid base of evidence supporting the usage of TEF will require more large-scale randomized controlled trials.

List of Abbreviations EN GER IG LT PEG QOL RTU TEF

Enteral nutrition Gastroesophageal reflux Intragastric Liquid and thickener Percutaneous endoscopic gastrostomy Quality of life Ready to use Thickened enteral formula

*Email: [email protected] Page 1 of 15


Introduction Thickened enteral formula (TEF) – defined here as a formula in which the viscosity is intentionally increased using thickener – is administered to prevent enteral nutrition (EN)-related complications, such as nausea, vomiting, and gastroesophageal reflux (GER). As no official definition of TEF has yet been proposed, it is also referred to as semi- or half-solid formula. Several studies have been conducted thus far in an attempt to describe the efficacy of TEF with viscosity ranging from 900 mPa s (similar to pancake syrup) to 20,000 mPa s (similar to tomato paste) (Ichimasa and Ichimaru 2010). Despite an incomplete understanding of precisely how TEF inhibits EN-related complications, its administration in place of liquid formula is becoming common practice in Japan. This chapter provides an overview of TEF, including its history, types available, suggested mechanism, and potential benefits.

History of TEF Enteral formulas are generally liquid in phase to allow administration through small-diameter tubes (e.g., 8–12 Fr). Liquids flow relatively easily, a property which may be responsible in part for observed EN-related complications. The usage of TEF was initially proposed to reduce the outflow of gastric contents by increasing the viscosity of enteral formula. Since its introduction by Inada et al. in 1998, TEF has been the subject of a number of clinical case studies presented at nutritional academic meetings. Improvements in EN-related complications, such as diarrhea and GER, have been reported with TEF compared with wholly liquid enteral formula. In addition, TEF has been reported able to be safely administered via intermittent or bolus methods. In chronic-stage patients, intermittent or bolus feeding is preferred to continuous feeding, as these methods avoid prolonging the immobility of patients, reduce the risk of pressure ulcers, and increase the time available for rehabilitation. While the positive effects of TEF on preventing diarrhea and GER are considered to be due to its high viscosity, which reduces the outflow of gastric contents, two studies have reported an increased gastric emptying rate following intake of a TEF compared with a liquid enteral formula (Shimoyama et al. 2007; Nagasawa 2009). These findings suggest that any improvement in preventing complications of EN observed with TEF is likely associated not only its high viscosity to resist the flow but also its effects on gastric motility. The mechanism of such inhibition of EN-related complications by TEF is still being investigated, with results of previous studies on the efficacy of TEF summarized in Table 1.

Types of TEF Three types of TEFs have been developed for clinical use, and their properties are described below.

Type 1: Intragastric Thickened Enteral Formula (IG-TEF) With IG-TEF, liquid thickener is administered through a feeding tube in advance, and the viscosity of the formula is later increased inside the stomach (Fig. 1). This type of TEF is primarily administered in patients with both nasogastric and gastrostomy tubes. The only type of thickener commercially available at present is REF-P1 ® (Kewpie Corporation, Tokyo, Japan). Pectin in REF-P1 ® forms a gel by binding divalent metal cations such as calcium. The ultimate viscosity of Page 2 of 15

17 Cerebrovascular disease, dementia

ND

900a

+

+

9/15

+ 14/ 15 9/14 7/9

10,000a 2,000a

X-ray

Symptoms

2,000b

Stepwise 20,000a intervention

Esophageal pH monitoring

Scintigraphy

Symptoms

+

+

Symptoms

Esophageal pH monitoring Esophageal pH monitoring

4/7

Symptoms

CT

Esophageal pH monitoring

Symptoms

+

+

4/8

2,000b

Pudding-like

3,000a

1,200a

12/15

2/4

+

+

+

+

+

Thickened barium

RTU

RTU

LT

IG

LT or RTU

LT

IG

IG

ND

ND

ND

ND

B

B

ND

B

ND

ND

ND

ND

ND

20

6

ND

ND

ND

ND

25

25

ND

23

25

ND

20

20

Temperature ( C)

400 ml

150 or 200 g

150 g

200 ml

ND

ND

400 ml

400 ml

400 ml

Amount of formula administered at a time

5–15 min

10 min

10 min

Bolus

30 min

ND

PEG

PEG

PEG

PEG

NGT

PEG or NGT

PEG

Oral

3 min

Bolus

PEG or NGT

56 (20–90) min

Duration of Feeding administration route

B B-type viscometer; CT computed tomography; GER gastroesophageal reflux; IG intragastric thickened enteral formula; LT thickened enteral formula prepared by adding thickener to liquid formula; ND not described; NGT nasogastric tube; PEG percutaneous endoscopic gastrostomy; RTU ready-to-use thickened enteral formula; TEF thickened enteral formula. “+” means present and “ ” means absent in statistical analysis. aMeasured by the author, bMeasured by the manufacturer

ND

Mean, 85.8 Crossover range, 56–100

Shizuku 32 Cerebrovascular et al. (2011) disease

15 ND

Mean, 83.1

Adachi 14 Cerebrovascular et al. (2009) disease

Goda (2006a)

Crossover

Mean, 82.7 6.8

Nishiwaki 15 Cerebrovascular et al. (2009) disease, dementia

Crossover

Crossover

Mean, 11.7 4.4

Leakage around the PEG tube

Crossover

Crossover

Type of TEF

Rotational speed Type of viscometer (rpm)

Modality to assess GER Diarrhea Fever Leakage complication Statistical analysis

Condition of viscosity measurement

Effectiveness of TEF

Before after 2,000b–20,000a 30/ Mean, 84.3 9.9 50 range, 57–101

Mean, 79.9 10.5

Viscosity

Before after 800–900a

Study design

Miyazawa 18 Cerebral palsy et al. (2008)

7

15 Intractable diarrhea

Yoshida 50 Aspiration et al. (2008) pneumonia

Kanie (2004b)

Mean, 21

Healthy volunteer

Tabei 4 et al. (2003)

Age

Mean, 72.5 range, 55–90

Profile

Inada 15 Cerebrovascular et al. (1998) disease, brain injury

Author year n

Subjects

Table 1 Previous studies evaluating the effectiveness of thickened enteral formula


Page 3 of 15


Thickened

1. Liquid thickener is administered. 2. Liquid enteral formula is administered. 3. Formula is thickened in the stomach.

Fig. 1 IG-TEF. Liquid thickener is administered through a feeding tube in advance, and the viscosity of the formula is later increased inside the stomach. This type of TEF is primarily administered in patients with both nasogastric and gastrostomy tubes. IG-TEF intragastric thickened enteral formula

Liquid formula

Thickener

Thickened Fig. 2 LT-TEF. Liquid formula is mixed with powder or liquid thickener and then manually administered through a feeding tube using a syringe. This type of TEF is primarily administered in patients with gastrostomy tubes. LT-TEF thickened enteral formula prepared by mixing liquid enteral formula and thickener

the TEF therefore depends on the calcium concentration in the liquid formula. For example, while the viscosity of an elemental formula (K-3S ®; Kewpie Corporation) is only 8 mPa s, the value increases to 900 mPa s within 10 min of adding 90 g of REF-P1 ® to 400 mL of the elemental formula (Inada et al. 1998).

Type 2: TEF Prepared by Mixing Liquid Enteral Formula and Thickener (LT-TEF) With LT-TEF, liquid formula is mixed with powder or liquid thickener and then manually administered through a feeding tube using a syringe (Fig. 2). This type of TEF is primarily administered in patients with gastrostomy tubes, which have a wide internal diameter to prevent tube occlusion. Thickening enteral formulas using the standard thickener for dysphagia patients to drink liquids often proves difficult, as EN formulas are higher in protein and fat than water, fruit juices, and other typical beverages. As such, several special thickeners for TEF have been developed which increase viscosity by reacting with the protein included in enteral formulas. Common thickeners for TEF available on the market are listed in Table 2. Most thickeners include dextrin or a polysaccharide thickener. Dextrin is made up of any of a number of various polysaccharides obtained by hydrolysis of starch and used as thickener not only in food manufacturing Page 4 of 15

a

NA not available Okada (2007)

Reflunon ® Reflunon Powder PG ®

Toromi perfect EN ® Easygel ®

Tsururinko for Liquid Diet ® Faset Powder ®

Softia ENS ®

Product Pegmelin ®

Powder Dextrin, xanthan gum, carrageenan, sodium citrate Powder Dextrin polysaccharide thickener pH control chemicals Powder Dextrin, polysaccharide thickener, sodium gluconate Liquid Maltodextrin, pectin, sodium citrate, sodium metaphosphate, pH control chemicals, calcium lactate Liquid Dextrin, polysaccharide thickener Powder Dextrin, polysaccharide thickener 13–38 1.3–4

27

4.8

1.0 11.1

1.5–2

1–2

10.8 23.3

1.5–4.5

2.8

Dosage to 100 mL of liquid formula (g) 3

12.9

Form Contents Powder Dextrin, polysaccharide thickener, potassium chloride Powder Dextrin, agar polysaccharide thickener 27.3

Fiber content g/100 g 1.5–3

Table 2 Examples of commercially available thickeners for thickened enteral formula

B

620–41,000a

5,000–10,000 B 1,000–10,000 B

NA

B

4,500–9,000

900–12,000

12 12

12

NA

12

25 25

20

NA

20

Healthy food Healthy food

Nisshin OilliO Otsuka

Food Care

Condition of viscosity measurement Expected Rotational viscosity Type of speed Temperature (mPas) viscometer (rpm) ( C) Manufacturer 2,000–10,000 B 12 20 Sanwa Kagaku 8,900 B 12 20 NUTRI 15,970 6 800–13,000 B 12 20 Clinico


Page 5 of 15


Fig. 3 RTU-TEF. Pre-thickened TEF is packed into a pouch with a spout that connects to the feeding tube and is administered by manually squeezing the pack. This type of TEF is primarily administered in patients with gastrostomy tubes. RTU-TEF ready-to-use thickened enteral formula

but also in pharmaceuticals. Polysaccharide thickener is the name given to a food additives mixture of two or more thickeners, such as pectin, carrageenan, guar gum, and xanthan gum, the blending ratio of which depends on each product. Cooking agar can also be used as a TEF thickener, but the need to dissolve the compound in boiling water before mixing with liquid formula renders it more troublesome to use than other agents. Gelatin is not used to thicken TEF because it melts at human body temperature and loses its viscosity easily. While the amount of thickener required to obtain an expected viscosity differs by product, the ultimate viscosity of LT-TEF can be additionally influenced by formula energy density, stirring time, and time elapsed since preparation (Wakita et al. 2012).

Type 3: Ready-to-Use TEF (RTU-TEF) Pre-thickened TEF is packed into a pouch with a spout that connects to the feeding tube and is administered by manually squeezing the pack (Fig. 3). Like LT-TEF, this type of TEF is also primarily administered in patients with gastrostomy tubes. RTU-TEF does not require a delivery container or administration set and is administered in a closed system. Given that elderly caregivers with a weak grip may find the pouch difficult to squeeze, a pressure bag similar to an arterial line pressure bag is sometimes used instead of manual squeezing. Common commercially available RTU-TEFs are listed in Table 3. The viscosity, energy density, and water concentrations of RTU-TEFs vary widely. The lack of a standardized method of measuring the viscosity is one drawback to using this type of TEF, with viscosity presently measured based on each manufacturer’s own conditions. As such, efficacy of RTU-TEF should not be based solely on quantitative viscosity data.

Potential Advantages of TEF While several advantages in using TEF have been reported, factors preventing EN-related complications are not fully understood, with further investigation yet needed to clarify just how TEF improves upon liquid formula administration. The following section addresses, at least in part, details of these factors.

Page 6 of 15

1.5 kcal/g

1.5 kcal/g

1.8 kcal/g

Recovery 5,000 Nutreat ® ACURE ® VF-5 5,000

5,000 10,000 6,000

6,000

Act Through ®

Hine Jerry AQUA ®

0.8 kcal/g

1.0 kcal/g

41.2

1.0 kcal/g

2,000

F2 Shot EJ ®

Hine Jerry ®

42

0.55 kcal/g 0.75 kcal/g

2,000 2,000

101

76

31

77

150 110

17

2.5 kcal/g

2,000

27.1

2.0 kcal/g

2,000

Water content (ml/100 kcal) 41.2

MEDIF ® PUSH CARE ® MEDIF ® PUSH CARE ® 2.5 F2 Light 55 ® F2 Light ®

Viscosity Energy Product (mPas) density ACURE ® VF-1 1,000 1.5 kcal/g

1.2

1.2

2

2.3

1.5

1.5

2.1 1.6

1.2

Agar, guar gum

Agar, guar gum

Agar, polysaccharide thickener Polysaccharide thickener

Agar

Pectin, agar

Pectin, agar Pectin, agar

None

Fiber content (g/100 kcal) Thickener 2.3 Polysaccharide thickener 1.2 None

Table 3 Examples of commercially available ready-to-use thickened enteral formulas

B

B

B

B

B

B

B B

B

B

12

12 6 12

12

12

6

6 6

6

6

20

20

20

20

25

25

25 25

25

25

250 g

300 g

167 g, 222 g

545 g 400 g, 533 g 200 g, 300 g, 400 g 200 g, 267 g 200 g, 267 g

150 g, 200 g 120 g, 160 g

Condition of viscosity measurement Type of Rotational Temperature Volume viscometer speed (rpm) ( C) per pack B 12 20 200 g

(continued)

Otsuka Pharmaceutical Factory Otsuka Pharmaceutical Factory

CLINICO

Asahi Kasei

Sanwa Kagaku

TERUMO

TERUMO TERUMO

AJINOMOTO

AJINOMOTO

Manufacturer Asahi Kasei


Page 7 of 15

NA not available

Semi Solid Support ®

PG Soft EJ ®

Calm Solid 500 ®

Calm Solid 400 ®

Product Calm Solid 300 ®

20,000

Viscosity (mPas) 10,000 20,000 10,000 20,000 10,000 20,000 20,000

Table 3 (continued)

2.0 kcal/mL

1.5 kcal/g

1.25 kcal/mL

1.0 kcal/mL

33

44

62.6

83.3

Energy Water content density (ml/100 kcal) 0.75 kcal/mL 116.3

1.9

0.37

1.3

1.3

Agar

Pectin, agar

Gelatinizer (hydrocolloids)

Gelatinizer (hydrocolloids)

Fiber content (g/100 kcal) Thickener 1.3 Gelatinizer (hydrocolloids)

B

6

20

Condition of viscosity measurement Type of Rotational Temperature viscometer speed (rpm) ( C) B 12 20 6 B 12 20 6 B 12 20 6 B 6 25

200 g, 267 g 200 mL, 250 mL

436 g (400 mL)

428 g (400 mL)

Volume per pack 420 g (400 mL)

Nestle Japan

TERUMO

NUTRI

NUTRI

Manufacturer NUTRI


Page 8 of 15


Prevention of GER Aspiration pneumonitis induced by GER is a serious problem for patients on tube feeding, and several studies examining TEF with viscosity ranging from 900 to 20,000 mPa s have shown the efficacy of TEF in preventing GER in this range (Table 1). Findings in a study using thickened noncaloric barium suggest that higher viscosity is thought to be more effective in preventing GER (Goda 2006a). However, the impact of the thickened noncaloric barium on the gut may differ from that of TEF, possibly due to the fact that noncaloric barium’s lack of fat and protein may not allow it to effectively stimulate the secretion of gut hormone, unlike TEF. Inada et al. (1998) and Tabei et al. (2003) reported on a population of patients on tube feeding for whom recurrent aspiration pneumonitis due to GER and incidence of pyrexia due to respiratory infections were ameliorated by administration of TEF with viscosity of 800–900 mPa s (no statistical analysis conducted). In contrast, however, Adachi et al. (2009) reported that TEF with viscosity of 2,000 mPa s had no positive effect on GER and in fact tended to increase incidence of acidic GER in patients with percutaneous endoscopic gastrostomy (PEG) feeding using the esophageal pH monitoring method. These controversial findings may be due to a lack of standardization in modalities for measuring viscosity and assessing complications. Compounding the confusion aroused by these conflicting findings is the fact that the mechanism by which TEF reduces GER is unclear. A study conducted on 11 healthy adult volunteers suggested that gastric emptying was accelerated by orally administered TEF with viscosity of 900 mPa s compared with standard liquid formula (Shimoyama et al. 2007). Findings showed that while the liquid formula initially entered the duodenum more rapidly from the stomach than TEF, once a certain volume was reached, gastric emptying was inhibited compared with that in subjects administered TEF. The authors stated that the mechanism of this inhibition of gastric emptying may have been the so-called “duodenal brake” triggered by increased blood levels of cholecystokinin. This early gastric emptying of TEF may contribute to preventing GER. However, conflicting results were reported in another study involving healthy subjects, which found that higher viscosity (16,000 and 128,000 mPa s) was associated with slower gastric emptying (Kawasaki et al. 2010). Similarly, a crossover study conducted on 15 post-PEG patients with history of aspiration pneumonia or vomiting noted no significant differences in gastric emptying time between those fed liquid formula and those receiving TEF, although GER was significantly decreased in those receiving the pudding-like viscosity TEF (Nishiwaki et al. 2009). These authors further suggested that TEF may prevent GER by improving its transition from the proximal to distal stomach. Further studies will be needed to more clearly understand this mechanism.

Prevention of Diarrhea Several clinical case studies have been published on prevention of diarrhea using TEF with viscosity ranging from 3,000 to 20,000 mPa s (Ito et al. 2006; Murabayashi et al. 2006; Nakayama et al. 2010). For example, improvement of intractable diarrhea was reported in 12 of 15 patients on liquid enteral nutrition after the introduction of TEF with viscosity of 6,000–20,000 mPa s (Yoshida et al. 2008). In contrast, however, a crossover study conducted on 32 post-PEG patients found no significant difference in the percentage of days with diarrhea between patients receiving RTU-TEF with viscosity of 2,000 mPa s and those on liquid formula (Shizuku et al. 2011). This discrepancy may be due to differences in study design and definition of diarrhea. Some of the benefits observed with TEF may be attributable in part to the soluble fiber content of the formula, which may delay small intestine transit time and help control diarrhea by increasing

Page 9 of 15


sodium and water absorption (Klosterbuer et al. 2011). Further research will be needed to confirm this effect or clarify some alternate mechanism.

Prevention of Leakage Around the PEG Puncture Site One of the late complications following PEG tube placement is leakage from the tube insertion site. A case report of an 85-year-old woman reported that nutrient leakage from the PEG insertion site was resolved immediately after starting TEF feeding (Kanie et al. 2004a). Similarly, Yoshida et al. (2008) found that the replacement of liquid formula with TEF suppressed leakage of gastrointestinal fluid in 4 of 7 patients. While logic suggests that leakage would naturally be reduced or resolved completely with TEF administration because of increased viscosity, helping to stem the flow, few clinical studies have been conducted to prove this effect.

Effects on Glucose Metabolism One case report described improvement of high blood glucose levels in a bedridden patient with diabetes mellitus on receiving TEF (Akatsu et al. 2005). In another study, 10 post-PEG patients showed significant reductions in blood glucose level at 60 and 120 min after initiation of feeding when administered TEF for 15 min than when fed liquid formula for 60 min (Goda 2006b). Dietary fibers in thickener may increase the viscosity of the chyme, thereby slowing the rate of intestinal glucose absorption (Hallfrisch and Behall 2000). In contrast, however, plasma glucose levels in healthy subjects were significantly higher after oral intake of TEF than with liquid formula (Shimoyama et al. 2007), a discrepancy in findings which may be due to inconsistencies in feeding manner and nutritional makeup between studies. Accurate comparison of the effects on glucose metabolism between TEF and liquid formula will require ensuring that the nutrient components and feeding manner are uniform.

Improvement of Quality of Life (QOL) in Patients and Caregivers

TEF is generally administered by bolus method. In a home care setting, 354 131 mL of TEF was administered once over 16.6 8.8 min (Okada and Ogawa 2011). Continuous feeding is often recommended with liquid enteral formula in order to minimize the incidence of EN-related complications during nutritional support. However, this method increases the time patients must remain in a sitting position, which may cause potential problems such as pressure ulcers or insufficient time allocated for rehabilitation. TEF allows for rapid administration of nutrients, potentially helping prevent the occurrence of pressure ulcers (Miyamoto 2009; Nakayama et al. 2010). TEF can also reduce the workload of nursing stuff and caregivers who typically must carefully observe patients during EN feeding. Time required for preparing and delivering formula, administering nursing care, and keeping an eye on patients receiving TEF was significantly reduced compared with time required to care for patients on liquid formula (Shizuku et al. 2011; Okada and Ogawa 2011). Cost expenditures may be reduced as well by using RTU-TEF, which requires no delivery container or administration set.

Unresolved Issues with TEF Ideal Viscosity The optimum viscosity of TEF remains unclear. In a clinical study conducted on post-PEG patients comparing those receiving one of two TEFs with viscosities of 4,000 of 10,000 mP s (viscosity measured under the same conditions), no significant differences were observed in length of hospital Page 10 of 15


stay or respiratory or gastrointestinal complications (Ichimaru et al. 2012). Several studies of TEF have been performed with viscosities ranging from 900 to 20,000 mP s; however, the efficacy of TEF should not be evaluated based solely on quantitative viscosity values, as modalities for measuring viscosity and assessing complications have not been standardized among studies (Table 1). A study evaluating the physical property of TEFs in artificial gastric juice found that when the isoelectric point of the constituent proteins was lower or higher than the pH of TEF, its viscosity tended to increase or decrease, respectively (Takemura et al. 2011). Maruyama et al. (2008) also reported that the properties of TEF depend on the acidity of gastric juice, which can be altered by H2 blockers. Changes in physical properties of TEF after administration into the stomach need to be considered to accurately compare the effectiveness of TEF.

Risk of Bacterial Contamination LT-TEF preparation involves mixing liquid formula with thickener and pouring the subsequent product into a syringe, a process which raises the risk of bacterial contamination. The environment in which thickener is added to TEF should therefore be controlled in order to reduce this risk. Of note, because IG-TEF and RTU-TEF need no such mixing, these two types of TEF have comparatively low risk for bacterial contamination.

Ideal Feeding Tube Type Two important points to consider when administering TEF through a feeding tube include the tube diameter and shape. IG-TEF can be used for a small-diameter nasogastric tubes, as the liquid thickener and liquid formula are administered into the stomach separately and the viscosity increases subsequent to administration. In contrast, LT-TEF and RTU-TEF are administered mainly via gastrostomy tubes because these formulas are thickened before administration and wide-internaldiameter tubes are necessary to prevent tube occlusion. Patients with low-profile PEG require extension tubes for bolus feeding with straight adaptors to administer TEF; an extension tube for continuous feeding with a 90 adaptor is not appropriate for TEF.

Ideal Volume and Timing of Additional Water Water content of RTU-TEF varies widely (Table 3). Energy-dense RTU-TEFs are not intended to meet the patient’s total fluid needs, and additional water should therefore be provided through a feeding tube for adequate hydration. However, if water is given immediately after TEF, the viscosity of TEF may be lowered in the stomach, thereby reducing the formula’s effectiveness. To ensure TEF efficacy, supplemental water is administered either more than 2 h before or more than 2 h after TEF administration. When additional fluid needs to be given immediately after TEF, thickened water should be administered via the feeding tube not to decrease the viscosity of TEF. Pre-thickened water packed into a pouch with a spout to connect to gastrostomy tubes is also available commercially. In addition, as little water as possible should be used when flushing the feeding tube to avoid decreasing the viscosity of TEF.

Nutrient Interactions: Malabsorption of Dietary Minerals Miura et al. (2008) examined the mineral concentration in the urine, excrement, and blood from rats following 2-week administration of liquid formula containing the same mineral composition as a TEF. Absorption of zinc, copper, iron, calcium, magnesium, sulfur, and potassium was lower in animals receiving TEF than in those on a liquid enteral formula. Although these authors’ conclusions need to be confirmed in humans, this potential negative effect of TEF should be kept in mind. Page 11 of 15


Table 4 Indications for application of thickened enteral formula TEF should be considered for use in patients who 1. Want to reduce time required for feeding to reserve time for rehabilitation 2. Repeat aspiration or vomiting 3. Repeat diarrhea without malabsorption 4. Have trouble with leakage from the PEG puncture site in the stomach 5. Have a gastrostomy tube due to head-and-neck cancer 6. Are stable but chronically ill and want to reduce the time required for feeding because they cannot stay in bed Reference: Goda (2011)

Applications to Critical or Intensive Care No data have yet been generated on the effects of TEF administration in critically ill patients. Generally, TEF is not suitable for this population, as pump-assisted continuous feeding is preferred in these patients and enhances gastrointestinal tolerance. Almost all kind of TEFs include fiber as a thickener, and data supporting the routine use of fiber in enteral feeding in critically ill patients are insufficient at present. The American Society of Enteral and Parenteral Nutrition (ASPEN) has stated that both soluble and insoluble fiber should be avoided in patients at high risk for bowel ischemia or severe dysmotility (McClave et al. 2009).

Applications to Other Conditions TEF administration is only successful with optimal gastric motor function and normal enterokinesis, digestion, and absorption. Indications of TEF reported as expert opinion are shown in Table 4 (Goda 2011). TEF appears to be most suitable for administration in patients with gastrostomy tubes in longterm care hospitals, nursing homes, or home medical care settings rather than acute care hospitals. Bolus feeding of TEF is contraindicated for patients with jejunostomy.

Guidelines and Protocols Few studies attempted to establish guidelines for TEF, nor is TEF cited in any guidelines published by major nutritional associations such as the European Society for Clinical Nutrition and Metabolism or American Society for Parenteral and Enteral Nutrition. At present, TEF is used based on expert opinions or practical experience. Most previous studies on TEF have been empirical, with little scientific evidence available supporting the efficacy of TEF. Compounding this dearth of supportive data is the fact that design characteristics such as viscosity of TEF, methods of assessing complications, and type of thickener used vary among studies, hampering understanding the mechanism of TEF. More large-scale randomized controlled trials should be conducted to clearly explain how TEF works, who benefits from its usage, and which viscosity is optimal.

Summary Points • Thickened enteral formula (TEF) is a formula in which viscosity is intentionally increased to prevent EN-related complications. Page 12 of 15


• Three types of TEF are available at present: intragastric TEF, TEF prepared by mixing liquid formula and thickener, and ready-to-use TEF. • Potential advantages of TEF are the prevention of gastroesophageal reflux, diarrhea, and skin trouble around the PEG puncture site and improvement of blood glucose levels and quality of life for both patients and caregivers. • However, the mechanism by which TEF exerts its effects and the optimum viscosity of TEF remain unclear. • When applying TEF, bacterial contamination, shape of a feeding tube, the timing and volume of additional water, and nutrient interactions should be considered. • At present, TEF can be used only in stable chronically ill patients with optimal gastric motor function, normal enterokinesis, digestion, and absorption. • Additional research is needed to identify the effectiveness, mechanism, and indications of TEF.

References Adachi K, Furuta K, Morita T, et al. Half-solidification of nutrient does not decrease gastroesophageal reflux events in patients fed via percutaneous endoscopic gastrostomy. Clin Nutr. 2009;28:648–51. Akatsu H, Yamamoto T, Suzuki Y, Kanie J. Better control of blood sugar with treatment using halfsolid nutrients: a case report [in Japanese]. Nihon Ronen Igakkai Zasshi. 2005;42:564–6. Goda F. The method of and evidence of short time gastrostomy tube feeding of semi-solid enteral nutrient. In: Goda F, editor. Guidebook for short time gastrostomy tube feeding of semi-solid enteral nutrient – towards the quality of good life for gastrostomy patients [in Japanese]. 1st ed. Tokyo: Ishiyaku Publishers; 2006a. p. 19–26. Goda F. The evidence for effectiveness of short time gastrostomy tube feeding of semi-solid enteral nutrient. In: Goda F, editor. Guidebook for short time gastrostomy tube feeding of semi-solid enteral nutrient – towards the quality of good life for gastrostomy patients [in Japanese]. 1st ed. Tokyo: Ishiyaku Publishers; 2006b. p. 27–34. Goda F. Short time gastrostomy tube feeding of semi-solid enteral nutrient [in Japanese]. In: PDN lectures. PEG doctors network; 2011. http://www.peg.or.jp/lecture/enteral_nutrition/05-02-01. html. Accessed 29 Apr 2013. Hallfrisch J, Behall KM. Mechanisms of the effects of grains on insulin and glucose responses. J Am Coll Nutr. 2000;19:320–25S. Ichimasa A, Ichimaru S. Review of mechanism, current evidence and practice of enteral semi-solid formula use to prevent gastroesophageal reflux, diarrhea, and to improve patient care [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2010;25:1207–16. Ichimaru S, Amagai T, Wakita M, Shiro Y. Which is more effective to prevent enteral nutritionrelated complications, high- or medium-viscosity thickened enteral formula in patients with percutaneous endoscopic gastrostomy?: a single-center retrospective chart review. Nutr Clin Pract. 2012;27:545–52. Inada H, Kaneda K, Yamagata N. Prevention of aspiration pneumonia in patients with gastroesophageal reflux using REF-P1 (pectin gel) [in Japanese]. Jpn J Parenter Enteral Nutr. 1998;20:1031–6. Ito Y, Imataka T, Kobayashi K, et al. Comparison of the thickening agent and agar to use to prepare half solid enteral nutrition for the purpose of prevention of gastroesophageal reflux [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2006;21:77–83. Page 13 of 15


Kanie J, Suzuki Y, Akatsu H, Kuzuya M, Iguchi A. Prevention of late complications by half-solid enteral nutrients in percutaneous endoscopic gastrostomy tube feeding. Gerontology. 2004a;50:417–9. Kanie J, Suzuki Y, Iguchi A, Akatsu H, Yamamoto T, Shimokata H. Prevention of gastroesophageal reflux using an application of half-solid nutrients in patients with percutaneous endoscopic gastrostomy feeding. J Am Geriatr Soc. 2004b;52:466–7. Kawasaki N, Urashima M, Odaira H, Noro T, Suzuki Y. Effects of gelatinization of enteral nutrients on human gastric emptying. Gastroenterol Res. 2010;3:106–11. Klosterbuer A, Roughead ZF, Slavin J. Benefits of dietary fiber in clinical nutrition. Nutr Clin Pract. 2011;26:625–35. Maruyama M, Hiroi J, Matsumura A, Hashimoto N, Yokoshima Y. Intra-gastric change of the semisolid formula with pectin liquid, “REF-P1” [in Japanese]. Jpn J Cancer Chemother. 2008;35:29–31s. McClave SA, Martindale RG, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). J Parenter Enteral Nutr. 2009;33:277–316. Miura Y, Endo R, Ikeda K, Sera K, Suwabe A. Comparison of absorption of trace elements on liquid and partially solidified enteral nutrition consist of the same elements – Examination about receipt and disbursement balance of trace elements after partially solidified enteral nutrition administration to rats. Nishina Mem Cyclotron Center Annu Report [in Japanese]. 2008;15:128–34. Miyamoto H. Application of nutrition support using half solid diet in the oldest patients with tube feeding [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2009;24:807–9. Miyazawa R, Tomomasa T, Kaneko H, Arakawa H, Shimizu N, Morikawa A. Effects of pectin liquid on gastroesophageal reflux disease in children with cerebral palsy. BMC Gastroenterol. 2008;8:11. Murabayashi Y, Simizu A, Sakuma T, et al. Clinical experience with addition of polysaccharides thickening agent to liquid formula diets [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2006;21:85–9. Nagasawa K. Influence of semi-solid nutrient on gastric emptying in patients with gastrostomy. Jpn J Appl Physiol [in Japanese]. 2009;39:297–302. Nakayama T, Hayashi S, Okishio K, et al. Prompt improvement of a pressure ulcer by the administration of high viscosity semi-solid nutrition via a nasogastric tube in a man with tuberculosis: a case report. J Med Case Reports. 2010;4:24. Nishiwaki S, Araki H, Shirakami Y, et al. Inhibition of gastroesophageal reflux by semi-solid nutrients in patients with percutaneous endoscopic gastrostomy. J Parenter Enteral Nutr. 2009;33:513–9. Okada S. Gel-forming properties of “EASYGEL”, the food for making various enteral nutrients into jelly [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2007;22:41–51. Okada S, Ogawa S. Influence of using semi-solid diet to the burden of nursing care for familycaregivers [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2011;26:1399–406. Shimoyama Y, Kusano M, Kawamura O, et al. High-viscosity liquid meal accelerates gastric emptying. Neurogastroenterol Motil. 2007;19:879–86. Shizuku T, Adachi K, Furuta K, et al. Efficacy of half-solid nutrient for the elderly patients with percutaneous endoscopic gastrostomy. J Clin Biochem Nutr. 2011;48:226–9. Tabei I, Kubo H, Yano F, Inada H. The effect of viscosity regulating solution for enteral nutrition against gastro esophageal reflux [in Japanese]. Jpn J Gastroenterol Surg. 2003;36:71–7. Page 14 of 15


Takemura Y, Yamashita S, Seiki M, Yamamoto T, Fukuda H. Changes in the physical properties of semisolid nutritional preparations in artificial gastric juice [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2011;26:1255–64. Wakita M, Masui H, Ichimaru S, Amagai T. Determinant factors of the viscosity of enteral formula – basic analysis of the thickened enteral formula. Nutr Clin Pract. 2012;27:82–90. Yoshida S, Minei K, Yoshimi Takenouch Y, Wakunami A. Nutrition support using semi-solid diet with tube feeding in hospitalized elder patients [in Japanese]. J Jpn Soc Parenter Enteral Nutr. 2008;23:43–9.

Page 15 of 15