Introduction
Percutaneous endoscopic gastrostomy (PEG) is a minimally invasive procedure for long-term
enteral tube feeding in patients with insufficient oral intake [1]
[2]
[3]. Although peristomal site infection is often noted as the most common adverse event
(AE) after PEG tube placement, it is seldom life-threatening and considered a minor
AE [4]. Feeding-related AEs have been identified as the main cause of death after PEG,
with up to 50 % of postoperative early mortality (30 days) being attributed to aspiration
pneumonia [5]
[6]. This may be related to the persistence of gastroesophageal reflux (GER) of enteral
feed after gastrostomy [7], even though PEG has been demonstrated to be superior to nasogastric tube feeding
in terms of preventing GER [8]
[9].
Recently, elemental diet (monomeric feed) has been shown to reduce the incidence of
aspiration pneumonia [10]. However, limitations such as high cost, high osmolality, and almost zero lipid
content may be an obstacle to the general use of this specialized feed. It has been
more than a decade since semi-solid feeds were developed as an alternative to conventional
liquid feeds to prevent feeding-related AEs [11]
[12]. Unfortunately, there is limited published literature on this topic despite the
wide usage of this feeding method in Japan. Amidst the growing popularity of this
method and the introduction of National Healthcare Insurance coverage for a semi-solid
feed prescription, we initiated a semi-solid feed protocol along with our existing
post-PEG feeding protocols in 2014. In this study (NCT02858596), we prospectively
evaluated the safety and efficacy of using semi-solid feed compared to conventional
liquid feed using clinical outcomes of interests such as the development of feeding-related
AEs, postoperative hospital length of stay and mortality.
Patients and methods
Study design and patients
Patients who received PEG for enteral nutrition at our hospital between January 2014
and December 2015 with the usage of gut (oral or nasogastric feeding) during the 2
weeks prior to procedure were allocated to receive a feeding protocol using either
liquid feed or semi-solid feed. Gastrostomy tube used was 20 Fr in size for all patients.
Patient allocation depended on the attending physician ordering the procedure with
most of the selection performed in a quasi-randomized manner. Patients with no recorded
gut usage 2 weeks prior to PEG were given a slower feeding protocol starting with
an oligomeric feed and not included in the study. This exclusion was to increase the
homogeneity between the intervention (semi-solid feed) and control (liquid feed) groups
in terms of baseline characteristics and protocol length. Likewise, procedure-related
mortality cases (< 1 %) were also excluded because the feeding protocol assigned could
not be sufficiently evaluated. [Fig. 1] summarizes the different postoperative feeding protocols used in our hospital.
Fig. 1 Feeding protocols after percutaneous endoscopic gastrostomy (PEG) in Hiroshima Kyoritsu
Hospital.
The total amount and daily increment of tube feeding calories and water as well as
the changes in parenteral nutrition used to supplement enteral feeding were the same
for both the liquid feed and semi-solid feed groups. However, the increment in calories
and water was stopped once daily requirements, as calculated by our nutrition support
team, were reached. The characteristics and nutrient data of enteral feed used are
shown in [Table 1], with the major difference being the dynamic viscosity of the feeds. Liquid feeds
were administered using gravity-controlled infusion (averaging 100 to 200 mL/hr) from
a ready-to-hang bag whereas semi-solid feeds were injected directly into the stomach
using a syringe via bolus infusion (5 to 10 minutes). For both groups, tube feeding
was conducted intermittently according to meal times with gravity-controlled water
administration (supplemented to match daily requirements) before infusion of feeds.
After discharge, patients receiving semi-solid feed continue to receive the same type
of prescription feed as currently covered by National Healthcare Insurance in Japan.
Table 1
Characteristics and nutrient data of enteral feed used.
|
Characteristics per 100 kcal
|
Liquid feed[1]
|
Semi-solid feed[2]
|
|
Total weight, g
|
100
|
66.7
|
|
Protein, g
|
4
|
4
|
|
Fat, g
|
2.8
|
2.2
|
|
Carbohydrate, g
|
14.5
|
16.1
|
|
Dietary Fiber, g
|
1
|
0.4
|
|
Water, ml
|
84.5
|
44
|
|
Dynamic viscosity, mPa·s (or cP)
|
5 – 10
|
20,000
|
1 Meiji’s Mei Balance 1.0 Z (Meiji Holdings Co.,Ltd., Tokyo, Japan)
2 PG Soft (Terumo Corporation, Tokyo, Japan)
Data regarding baseline characteristics such as age, gender, comorbidities, and preoperative
biomarkers (body mass index and blood laboratory markers collected on the day of procedure)
as well as postoperative findings such as laboratory biomarker changes at day 7 after
the procedure, AEs (feeding-related aspiration pneumonia, diarrhea etc.) and clinical
outcomes of interest (postoperative length of stay and mortality) were compared for
the 2 groups studied. Feeding-related aspiration pneumonia was diagnosed using clinical
symptoms, with confirmation through radiologic findings or detection of enteral feed
in the patient’s trachea aspirate. Peristomal infection was assessed 1 week after
the procedure using a previously validated scoring system (Jain’s infection score)
by assigning a score for erythema (0 to 4), induration (0 to 3) and exudate (0 to
4) [13]. Infection was defined as development of pus or a combined infection score of 8
or more. Diarrhea was evaluated using the King’s Stool Chart and feeding-related diarrhea
was defined as an absolute daily fecal score of 15 or more after ruling out other
causes such as drug-induced diarrhea or Clostridium difficile infection [14]. This study protocol was reviewed and approved by the ethics review committee of
Hiroshima Kyoritsu Hospital. All patients, or their legal guardians, provided written
informed consent for the procedures as well as enrollment in the study. The research
was carried out in accordance with Japan’s Ethical Guidelines for Epidemiological
Research (2008) and the Declaration of Helsinki (2013).
Statistical analysis
Continuous variables are expressed as mean (standard deviation with range occasionally).
Categorical variables are expressed as numbers (percentage). Comparisons for continuous
variables were made using the Student t-test for normal data and the Mann-Whitney U test for non-parametric data. Tests for
proportionality between groups were made using the chi-square test (or Fisher's exact
test when indicated). Logistic regression and analysis of covariance were used to
evaluate possible factors that may be associated with the development of feeding-related
aspiration pneumonia and postoperative length of stay. The number needed to treat
(and 95 % confidence interval) for feeding-related pneumonia was also calculated.
Statistical significance was defined as P < 0.05 and analysis was performed using XLSTAT2014 for Windows (Addinsoft Ltd., Paris,
France).
Results
In total, 117 patients (age range: 59 – 97 years, male: 53) were included in the study.
Seventy-two patients were given liquid feed protocols while 45 patients received semi-solid
feed protocols. Baseline characteristics of patients (age, gender, comorbidities and
preoperative biomarkers) are listed in [Table 2]. There were no significant differences at baseline, including the frequency of comorbidities
that may affect gastric motility such as previous gastric resection and hiatal hernia
(moderate size and above) between the 2 groups. Indications for PEG were primarily
dysphagia secondary to neurologic impairments or insufficient oral intake due to various
underlying conditions as listed in the comorbidities section.
Table 2
Baseline characteristics of patients.
|
Liquid feed
(n = 72)
|
Semi-solid feed
(n = 45)
|
P value
|
|
Age, years, mean (SD, range)
|
81.0 (9.1, 59 – 97)
|
80.7 (8.3, 61 – 95)
|
0.76
|
|
Gender (male/female)
|
33/39
|
20/25
|
0.88
|
|
Comorbidities
|
|
Stroke, n (%)
|
53 (73.6)
|
36 (80)
|
0.43
|
|
Antithrombotic therapy, n (%)
|
26 (36.1)
|
17 (37.8)
|
0.86
|
|
Dementia, n (%)
|
29 (40.3)
|
13 (28.9)
|
0.21
|
|
Neurodegenerative disorders, n (%)
|
11 (15.3)
|
7 (15.6)
|
0.97
|
|
Respiratory disorders, n (%)
|
35 (48.6)
|
19 (42.2)
|
0.50
|
|
Diabetes mellitus, n (%)
|
16 (22.2)
|
14 (31.1)
|
0.28
|
|
Pressure ulcer, n (%)
|
17 (23.6)
|
8 (17.8)
|
0.45
|
|
Malignancy, n (%)
|
11 (15.3)
|
5 (11.1)
|
0.52
|
|
Partial gastric resection, n (%)
|
2 (2.8)
|
1 (2.2)
|
1.00
|
|
Hiatal hernia (> moderate size), n (%)
|
2 (2.8)
|
2 (4.4)
|
0.64
|
|
Preoperative biomarkers
|
|
Body mass index, kg/m2, mean (SD)
|
17.9 (3.6)
|
18.0 (3.0)
|
0.67
|
|
Hemoglobin, g/dL, mean (SD)
|
11.6 (1.8)
|
11.3 (2.0)
|
0.52
|
|
Serum albumin, g/dL, mean (SD)
|
2.8 (0.5)
|
2.9 (0.6)
|
0.34
|
|
TLC, /μL, mean (SD)
|
1508 (863)
|
1532 (701)
|
0.61
|
|
C-reactive protein, mg/dL, mean (SD)
|
2.4 (2.9)
|
1.8 (2.7)
|
0.15
|
|
Total cholesterol, mg/dL, mean (SD)
|
152 (44)
|
151 (31)
|
0.82
|
|
Blood urea nitrogen, mg/dL, mean (SD)
|
23.7 (17.8)
|
22.8 (14.0)
|
0.75
|
|
PT-INR, mean (SD)
|
1.20 (0.23)
|
1.13 (0.11)
|
0.07
|
SD, standard deviation; TLC, total lymphocyte count; PT-INR, international normalized
ratio of prothrombin time.
[Table 3] summarizes the postoperative clinical course of patients after PEG tube placement.
Laboratory biomarkers were collected on postoperative day 7 and changes from preoperative
values were compared between the 2 groups, with no significant differences found.
Overall, feeding-related aspiration pneumonia was the most common AE, followed by
peristomal infection and feeding-related diarrhea. Compared to the Liquid feed group,
the Semi-solid feed group had a significantly lower incidence of aspiration pneumonia
(2.2 % vs. 22.2 %, P < 0.005). Using logistic regression, after adjusting for preoperative C-reactive
protein levels, patients in the Liquid feed group were more likely to develop feeding-related
aspiration pneumonia compared to those in the Semi-solid feed group (Adjusted odds
ratio 11.99, 95 % CI: 1.51 to 95.08, P < 0.05). After adjusting for preoperative serum albumin levels, the odds of developing
aspiration pneumonia was also higher in the Liquid feed group (Adjusted odds ratio
12.51, 95 % CI: 1.56 to 100.52, P < 0.05). The calculated number needed to treat using semi-solid feed for feeding-related
aspiration pneumonia was 5 patients (95 % CI: 3 to 13). Although not statistically
significant, there were fewer cases of feeding-related diarrhea in the Semi-solid
feed group as well. The frequency of peristomal infection and the average infection
scores were not significantly different between both groups. No tube obstruction was
observed in either groups.
Table 3
Postoperative clinical course of patients.
|
Liquid feed
(n = 72)
|
Semi-solid feed
(n = 45)
|
P value
|
|
Biomarker changes at day 7
|
|
∆ Hemoglobin, g/dL, mean (SD)
|
– 0.6 (0.9)
|
– 0.5 (1.2)
|
0.48
|
|
∆ C-reactive protein, mg/dL, mean (SD)
|
0.3 (3.8)
|
0.4 (3.2)
|
0.79
|
|
∆ Serum albumin, g/dL, mean (SD)
|
– 0.1 (0.3)
|
– 0.1 (0.4)
|
0.61
|
|
∆ Blood urea nitrogen, mg/dL, mean (SD)
|
– 0.8 (8.9)
|
0.6 (7.8)
|
0.95
|
|
Adverse events
|
|
Feeding-related aspiration pneumonia
|
16 (22.2)
|
1 (2.2)
|
< 0.005
|
|
Peristomal infection
|
9 (12.5)
|
5 (11.1)
|
0.82
|
|
Jain’s infection score, mean (SD)
|
1.5 (1.6)
|
1.2 (1.3)
|
0.24
|
|
Feeding-related diarrhea
|
9 (12.5)
|
1 (2.2)
|
0.09
|
|
Tube obstruction
|
0 (0)
|
0 (0)
|
N/A
|
|
Clinical outcomes
|
|
Length of stay, days, mean (SD)
|
18.8 (13.4)
|
12.7 (7.5)
|
< 0.01
|
|
In-hospital mortality
|
9 (12.5)
|
1 (2.2)
|
0.09
|
|
14-day mortality
|
3 (4.2)
|
1 (2.2)
|
1.00
|
|
30-day mortality
|
6 (8.3)
|
1 (2.2)
|
0.25
|
|
60-day mortality
|
9 (12.5)
|
2 (4.4)
|
0.20
|
|
90-day mortality
|
11 (15.3)
|
4 (8.9)
|
0.40
|
|
30-day readmission after discharge
|
3 (4.8)
|
0 (0)
|
0.05
|
Values expressed as n (%) unless otherwise specified. N/A: Not applicable.
Postoperative length of stay was significantly shorter in the Semi-solid feed group
(12.7 days vs. 18.8 days, P < 0.01). There were also fewer deaths (in-hospital, 14-day, 30-day, 60-day and 90-day)
in the Semi-solid feed group albeit not significantly different when compared to the
Liquid feed group. After discharge, patients in the Semi-solid group also seemed less
likely to be readmitted within the same month (0 % vs. 4.8 %, P = 0.05). As shown in [Table 4], analysis of covariance demonstrated that using semi-solid feed was associated with
a shorter postoperative length of stay even after taking into account age, gender,
preoperative serum albumin levels and preoperative C-reactive protein levels (β – 0.23,
95 %CI: – 0.41 to – 0.06, P < 0.01).
Table 4
Factors associated with postoperative length of stay (analysis of covariance).
|
Variable
|
β (95 % CI)[1]
|
P value
|
|
Age
|
0.09 (– 0.28 to 0.10)
|
0.35
|
|
Male gender
|
0.08 (– 0.12 to 0.27)
|
0.43
|
|
Preoperative serum albumin
|
0.02 (– 0.18 to 0.22)
|
0.84
|
|
Preoperative C-reactive protein
|
0.20 (0.01 to 0.40)
|
< 0.05
|
|
Semi-solid feed protocol
|
– 0.23 (– 0.41 to – 0.06)
|
< 0.01
|
1 Standardized coefficients with 95 % confidence interval using all variables listed
in table. (Model’s adjusted R
2 = 0.13; F5, 111 = 3.21, P < 0.01)
Discussion
PEG has been established as a safe and simple procedure for long-term enteral tube
feeding. Nevertheless, feeding-related AEs such as aspiration pneumonia from GER of
gastric feed may impede the successful use of PEG and contribute to postoperative
mortality. Although jejunal feeding may reduce GER, an additional procedure is required
and pump-assistance may also be necessary for enteral nutrition [15]. In Japan, the use of semi-solid feed in PEG patients to reduce feeding-related
AEs such as aspiration pneumonia, peristomal leakage, and diarrhea is quite common.
Semi-solid feed is considered to be more physiologic (swallowed food does not enter
the stomach in the liquid form) and is reported in Japanese literature to reduce the
incidence of GER, peristomal leakage, and diarrhea. Because it is given via bolus
infusion, patients and care-givers are less restricted during feeding time, which
may in turn contribute to a higher quality of life and lower incidence of pressure
ulcers.
In an animal model of gastroesophageal reflux disease (GERD), use of semi-solid feed
significantly reduced the frequency of GER during feeding and post-feeding periods
[16]. In PEG patients, the efficacy of semi-solid feed in decreasing or inhibiting GER
is not conclusive, with conflicting results being reported [17]
[18]
[19]. That may be due to differences in the dynamic viscosity of semi-solid feed used
in various studies. A recent study also demonstrated that use of semi-solid feed was
associated with fewer observational days with fever but the cause of fever in that
study was not clearly defined [20].
This study showed that PEG patients with a postoperative feeding protocol using semi-solid
feed had better clinical outcomes in terms of the frequency of feeding-related aspiration
pneumonia and postoperative hospital length of stay. Fewer feeding-related AEs such
as aspiration pneumonia in the Semi-solid feed group may have contributed to the shorter
postoperative length of stay. Multivariate analysis also showed that using semi-solid
feed had a positive effect on postoperative hospital length of stay, regardless of
age, gender, and preoperative nutritional as well as inflammation status. Tube obstruction
did not occur no matter which type of feed was used. The positive effect of using
semi-solid feed also seemed to extend beyond discharge, as shown in the 30-day hospital
readmission rates of both groups.
Even with the reduction in aspiration pneumonia, significant improvement in mortality
rates was not observed in the Semi-solid feed group. One possible explanation is that
the attending physicians were free to change the type of feed when patients encountered
feeding-related AEs. Further analysis revealed that 10 of 16 patients who had feeding-related
aspiration pneumonia in the Liquid feed group changed to semi-solid feeding upon resuming
enteral nutrition. Likewise, 4 of 9 patients who experienced feeding-related diarrhea
in the Liquid feed group also had their feed changed to semi-solid type. This could
be a reason why only postoperative length of stay (affected by AEs) was significantly
different between the 2 groups.
Notable limitations of this study include the probability of selection bias (only
quasi-randomized at best), which could explain why there were fewer patients enrolled
in the Semi-solid group. The study also lacks long term follow-up data beyond 90 days
(which is still in progress as an ongoing observational study). One potential disadvantage
of using semi-solid feed is the requirement for additional water supplementation.
As shown in [Table1], for the same amount of calories, semi-solid feed contains roughly half the water
contained in a typical liquid feed. There is concern that administration of larger
amounts of water may cause GER, resulting in aspiration. However, it has been demonstrated
that gastric emptying is usually faster for water and liquid with lower caloric content
[21].
Conclusion
This study demonstrated that using semi-solid feeds may reduce the risk of aspiration
pneumonia and shorten postoperative hospital length of stay after PEG. These clinical
outcomes may lead to a better quality of life for patients and lower medical costs.
Large-scale randomized controlled trials are warranted to confirm this. Semi-solid
feeds are safe to use and can be employed either as a first-line feeding protocol
or an alternative when liquid feeding is unsuccessful.
