Abstract
Patients with gastroparesis (Gp) not meeting nutritional needs orally, may need enteral nutrition (EN) or total parenteral nutrition (TPN). Among patients with gastroparesis, we aimed to: 1) Identify the frequency of EN and TPN use; and 2) Explore characteristics of patients with EN/TPN to those using oral nutrition (ON) including changes over 48 weeks.
Methods:
Gp patients enrolled in NIDDK Gastroparesis Registries underwent history and physical examination, gastric emptying scintigraphy (GES), water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms, and both general and Gp-related quality of life (QOL). Patients were followed 48 weeks after enrollment.
Results:
Of 971 patients with Gp (579 idiopathic [IGp], 336 diabetic [DGp], 51 post Nissen fundoplication [PNFGp]), 939 (96.7%) were using ON only, 14 (1.4%) using TPN, and 18 (1.9%) using EN. Compared to ON patients, TPN and EN patients were younger, had lower body mass index, and had greater nausea/vomiting, early satiety/postprandial fullness, and abdominal pain severity. Patients on TPN or EN had lower SF-36 physical QOL, but not mental QOL nor Gp-related QOL. TPN and EN patients ingested less water during WLST, but did not have worse gastric emptying. Of those who had been on TPN or EN, 50% and 25% respectively, resumed ON at 48-week follow-up.
Conclusions:
This study describes Gp patients requiring TPN and/or EN for nutritional support who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters associate with this subset which provide insight into use of nutritional support in gastroparesis.
Clinical Relevancy Statement
Total parenteral nutrition and/or enteral nutrition is used for nutritional support in 3% of patients with gastroparesis enrolled in the NIDDK Gastroparesis Registry. Independent factors that were associated with the need for total parenteral or enteral nutrition were low body weight, more severe symptoms of nausea, vomiting and early satiety, and use of narcotic analgesia. These patients had a poorer physical quality of life than gastroparesis patients on oral nutrition. Over 48 weeks, half or fewer of these patients resumed oral feedings for nutrition. Of Gp patients using oral nutrition at enrollment, 2.7% worsened to need total parenteral or enteral nutrition over 48 weeks follow up.
Keywords: enteral nutrition, parenteral nutrition, obesity, gastroparesis, idiopathic gastroparesis, gastric emptying
Introduction
Attention to nutrition is important in patients with gastroparesis (Gp), as they are prone to malnutrition due to symptoms of nausea, vomiting, and early satiation. Many gastroparesis patients on oral nutrition consume energy deficient diets (1). If the patient with gastroparesis is unable to consume adequate calories through a solid food diet, stepwise oral nutritional interventions could include use of homogenized meals, liquid meals as well as the addition of oral nutrition supplements (2,3).
If patients cannot meet nutritional needs orally, then enteral nutrition is considered. Enteral jejunostomy nutrition can be an option for patients who fail to stabilize their weight loss, or for those who cannot gain weight with oral feedings (4,5). Enteral feeding is preferred over parenteral nutrition for a range of practical reasons, such as costs, decreased potential for complications, and ease of delivery (2). A feeding jejunostomy tube, which bypasses the affected stomach, can improve symptoms and reduce hospitalizations (6). Jejunostomy tubes can be placed surgically or endoscopically, or by specialized gastrojejunostomy (G-J) tubes inserted endoscopically, radiologically, or surgically.
Total parenteral nutrition (TPN) is used if enteral feeding is not tolerated or is insufficient to meet caloric needs. TPN provides nutrients to a person's bloodstream through an intravenous (IV) infusion using a peripherally inserted central catheter (PICC), Hickman line, portacath, or some other central venous catheter. Use of TPN can have complications of thrombosis and infection, and TPN-associated liver disease, and only should be used in select cases where adequate nutrition through the intestinal tract is not possible (5).
Despite the use of enteral nutrition and TPN in gastroparesis, the frequency of use, associated patient characteristics, and clinical outcomes are not well described. In a large cohort of individuals with Gp, we aimed to: 1) Identify the frequency of EN and TPN; and 2) Explore characteristics of patients with EN/TPN to those using only oral nutrition (ON) including changes in nutritional needs over 48 weeks.
Methods
Overview
Patients with symptoms of Gp enrolled in the three NIDDK Gastroparesis Registry studies underwent history and physical examination, gastric emptying scintigraphy (GES) that defined Gp, water load satiety testing (WLST), and questionnaires assessing symptoms and quality of life. For each patient, the use of ON, EN, and TPN was recorded. Patients were followed up 48 weeks after enrollment. This retrospective analysis of the data collected for the NIDDK GpCRC Registry studies looks at patients who on enrollment had delayed GES.
Patient Enrollment
The NIDDK Gastroparesis Clinical Research Consortium (GpCRC) is a network of six adult clinical centers and a Scientific Data Research Center. Patients were enrolled in the Gastroparesis Registry 1,2,3 (ClinicalTrials.gov Identifiers: NCT00398801, NCT01696747, NCT03680859) which are observational studies of patients with gastroparesis (7) with entry criteria being 18 years or older with symptoms of at least 12 weeks, gastric emptying scintigraphy (GES) within 6 months of enrollment, and no structural abnormality as seen by upper endoscopy within one year of enrollment. The patients enrolled in the registry could have idiopathic, diabetic, or post-fundoplication gastroparesis. At each study visit (enrollment, 6 months, and 12 months), symptoms and treatments were assessed, questionnaires were filled out, and body weight and height along with waist and hip circumference were obtained, as well as nutrition sources. Patients received standard of care evaluations during follow-up, allowing adjustments or additions of treatments for their clinical care.
This descriptive cohort study was approved by the Institutional Review Board at each center and all participants provided informed consent. All authors had access to study data and reviewed and approved the final manuscript.
Study Protocol
During face-to-face interviews with each patient, study physicians or coordinators completed case report forms including data on gastroparesis disease onset, symptoms, body weight and height, waist and hip circumference, disease profile, associated medical conditions including diabetes, and medication and supplemental therapies, and number of hospitalizations over the prior year. Prior surgeries were inquired. Study physicians performed a physical examination including body weight and height.
Each patient filled out the Patient Assessment of Upper GI Symptoms (PAGI-SYM) questionnaire which assesses symptoms of gastroparesis, dyspepsia, and gastroesophageal reflux disease (8); it includes the nine symptoms of the Gastroparesis Cardinal Symptom Index (GCSI) (9). Patients were asked to assess the severity of their symptoms during the previous two weeks from 0 to 5 scaled as no symptoms=0, very mild=1, mild=2, moderate=3, severe=4, and very severe=5. PAGI-SYM subscale scores for upper GI symptoms were calculated for nausea/vomiting, postprandial fullness/early satiety, bloating, upper abdominal pain/discomfort and heartburn/regurgitation. Overall gastroparesis symptom severity was determined by the GCSI score, which averages the three subscores of nausea/vomiting, postprandial fullness/early satiety, and bloating subscores. The nausea/vomiting subscale score is the mean of scores for nausea, retching, and vomiting. The postprandial fullness/early satiety subscale score is the mean of scores for stomach fullness, not being able to finish a normal-sized meal, feeling excessively full after meals, and loss of appetite. The bloating/visible distention subscale score is the mean of scores for bloating and stomach or belly visibly larger.
Quality of life was assessed with two validated instruments. The Medical Outcomes Study 36-Item Short-Form Health Survey version 2 (SF-36v2) was used to assess the patients’ overall physical and mental health (10). Disease-specific quality of life during the prior 2 weeks was assessed by Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QOL) survey, which scores 30 factors from 0 (none of the time) to 5 (all of the time) (11). These scores are then reversed so that the higher PAGI-QOL scores is interpreted as better QOL.
Gastric Emptying Scintigraphy
Patients stopped medications that could affect gastrointestinal motility for 72 hours prior to the study and reported in the morning after fasting overnight. Diabetic patients had glucose checked to ensure <275 mg/dl. Gastric emptying scintigraphy was performed using standard low-fat, Eggbeaters® meal to measure solid emptying over 4 hours (12,13). Gastric retention of Tc-99m >60 % at 2 hours and/or >10% at 4 hours was considered delayed gastric emptying.
Water Load Satiety Test
Patients stopped medications that could affect gastrointestinal motility for 72 hours prior to the study and reported in the morning after fasting overnight. Diabetic patients had glucose checked to ensure <275 mg/dl. Subjects ingested water until they achieved the sensation of “completely full” during a five-minute time period (14). The volume of water ingested was recorded.
Statistical Methods
Patients were classified into ON if they were on ON only, and not EN or TPN. Patients were classified as EN if they were receiving EN with or without ON, but not on TPN. Patients were classified as TPN if there were receiving TPN, irrespective of the presence or absence of ON and EN. Baseline characteristics included age, sex, ethnicity, race, diabetes status, gastroparesis etiology, acute vs. insidious symptom onset, presence of initial infectious prodrome, hospitalization for gastroparesis in the year prior to enrollment, 2-hour and 4-hour gastric emptying retention (%), GCSI, SF-36 physical and mental scores. Baseline patient characteristics were compared by the nutritional sources of the patient at enrollment (ON, EN, TPN) and at 48-weeks. Data are presented as mean ± SD or N (%) or median (Q1, Q3) for measures with very skewed distributions. P values were determined by Fisher’s exact test for categorical measures and by analysis of variance (ANOVA), t-tests, or nonparametric Wilcoxon rank sum tests for continuous measures. Non-parametric tests were used when one or more of the subgroups had a skewed distribution. To identify characteristics independently associated with being on TPN/EN at any time, a forward and backward stepwise model selection approach using a minimum AIC criteria was applied to the following candidate variables: acute vs. insidious symptom onset, BMI, number of hospitalizations in prior year, PAGI-QOL overall score, narcotic use (yes/no), 4-hour GES gastric retention (%), and nausea/vomiting subscore, bloating subscore, early satiety/postprandial fullness subscore, and upper abdominal score. All p-values are two-sided and not corrected for multiple comparisons since these are exploratory analyses. Analyses were conducted using SAS 9.4 (15) and R version 4.0.3 (16).
Results
Participant Characteristics
971 patients with Gp (579 idiopathic [IGp], 336 diabetic [DGp], 51 post Nissen fundoplication [PNFGp]) have been enrolled in the NIDDK Gp registries. The average age was 43.9±14.2 years (7.2% ≥65; 0% ≥85 years), 84.1% were female with racial and ethnic background as follows: 8.9% Black, 14.9% Hispanic/Latino, 73.2% White, and 2.9% other. One patient did not provide race/ethnicity information. The average BMI was 27.6±7.5 kg/m2 with 7.8% of patients being underweight (BMI <18.5), 35.0% normal weight (BMI 18.5 – 24.9), 22.9% overweight (BMI 25.0 – 29.9), and 34.3% obese (BMI 30.0 or higher). BMI was strongly correlated with waist circumference (r=0.83l, p<0.001) and less well with the waist to hip ratio (r=0.35). The predominant symptoms were nausea in 30.7%, abdominal pain in 20.3%, vomiting in 20.1%, and bloating in 9.7%. The mean GCSI score was 3.0±1.1, with nausea/vomiting subscore 2.4±1.5, satiety/fullness subscore 3.4±1.2, and bloating/distension subscore 3.1±1.6. The upper abdominal score was 3.1±1.5. Medication and device use were as follows: 42.9% prokinetic medications, 32.1% narcotics, and 6.4% gastric stimulators.
Baseline
Of our 971 patients with gastroparesis, 939 (96.7%) were using ON only (555 IGp, 328 DGp, 51 PNFGp), 14 (1.4%) using TPN (13 IGp, 1 DGp), and 18 (1.9%) using EN (11 IGp, 7 DGp) (Table 1). Of the 14 patients on TPN, 2 also received EN, and 8 continued ON. Of the 18 patients on EN, 9 were also using ON.
Table 1.
Characteristics of Gastroparesis Patients according to Nutrition Source at baseline
| Parenteral Feedings | Enteral Feedings | Oral Feedings Only | P† | |
|---|---|---|---|---|
| N | 14 (1.4%) | 18 (1.9%) | 939 (96.7%) | |
| Demographics | ||||
| Age – mean (SD) | 36.3 (14.07) | 38.23 (11.84) | 44.08 (14.19) | 0.03 |
| Female Sex - no. (%) | 12 (85.7%) | 16 (88.9%) | 789 (84%) | 0.94 |
| Waist Circumference (cm) – mean (SD) | 82.9 (15.8) | 83.4 (17.2) | 92.1 (19.2) | 0.04 |
| Waist-To-Hip Ratio – mean (SD) | 0.91 (0.12) | 0.89 (0.12) | 0.89 (0.09) | 0.70 |
| Waist-To-Hip Ratio Health Risk – no. (%) | ||||
| Low | 3 (21.4%) | 6 (33.3%) | 221 (23.6%) | 0.46 |
| Moderate | 4 (28.6%) | 5 (27.8%) | 183 (19.5%) | |
| High | 7 (50.0%) | 7 (38.9%) | 534 (56.9%) | |
| BMI – mean (SD) | 23.75 (7.1) | 23.75 (4.77) | 27.74 (7.49) | 0.01 |
| Underweight | 4 (28.6%) | 1 (5.6%) | 71 (7.6%) | 0.03 |
| Normal | 5 (35.7%) | 11(61.1%) | 324 (34.5%) | |
| Overweight | 2 (14.3%) | 4 (22.2%) | 216 (23.0%) | |
| Obese | 3 (21.4%) | 2 (11.1%) | 328 (34.9%) | |
| Etiology – no. (%) | ||||
| Idiopathic, not DM | 13 (92.9%) | 11 (61.1%) | 555 (59.1%) | 0.25 |
| Diabetes | 1 (7.1%) | 7 (38.9%) | 328 (34.9%) | |
| Post-Nissen Fundoplication | 0 (0%) | 0 (0%) | 51 (5.4%) | |
| Symptoms – median (Q1, Q3) | ||||
| GCSI Score | 3.8 (2.8, 4.0) | 3.3 (2.8, 4.1) | 3.0 (2.3, 4.3) | 0.04 |
| Nausea subscore | 3.5 (2.4, 4.5) | 3.2 (2.7, 4.6) | 2.3 (1.0, 3.7) | 0.002 |
| Early Satiety Subscore | 4.1 (3.1, 4.5) | 4.3 (3.8, 4.5) | 3.5 (2.8, 4.3) | 0.006 |
| Bloating Subscore | 3.8 (2.3, 4.4) | 4.0 (0.6, 4.9) | 3.5 (2.0, 4.5) | 0.94 |
| Upper Abdominal Score | 4.0 (2.6, 5.0) | 4.0 (3.1, 4.0) | 3.0 (2.0, 4.0) | 0.03 |
| Lower Abdominal Score | 3.0 (2.5, 4.5) | 3.5 (3.0, 4.0) | 2.5 (1.5, 3.5) | < 0.001 |
| GERD Score | 1.9 (1.7, 3.0) | 2.7 (1.9, 3.4) | 1.9 (0.89, 3.0) | 0.07 |
| Quality of Life – median (Q1, Q3) | ||||
| SF-36 PCS | 25.7 (18.8, 31.8) | 24.2 (18.6, 30.9) | 33.0 (25.7, 41.0) | < 0.001 |
| SF-36 MCS | 32.7 (28.3, 41.0) | 38.8 (32.4, 54.2) | 40.2 (30.5, 49.5) | 0.21 |
| PAGI-QOL Overall | 1.9 (0.1, 3.3) | 2.1 (0.1, 4.2) | 2.6 (0, 5) | 0.02 |
| Gastric Physiology – mean (SD) | ||||
| % Gastric Retention, 2hrs | 62.0 (21.1) | 70.6 (19.8) | 65.9 (17.9) | 0.40 |
| % Gastric Retention, 4hrs | 38.3 (26.1) | 39.4 (22.7) | 33.4 (22.6) | 0.42 |
| Severe retention (4 hr R>35%) | 7/13 (53.8%) | 9/17 (52.9%) | 339/931 (36.4%) | 0.17 |
| Volume water for WLST (mL) | 169.0 (119.7) | 216.2 (169.3) | 393.6 (233.1) | 0.007 |
| Nutritional Sources - no. (%) | ||||
| Oral Feeding | 8/14 (57.1%) | 9/18 (50%) | 939/939 (100%) | < 0.001 |
| Enteral Feeding | 2/14 (14.3%) | 18/18 (100%) | 0/939 (0%) | < 0.001 |
| Parenteral Feeding | 14/14 (100%) | 0/18 (0%) | 0/939 (0%) | < 0.001 |
| Medications - no. (%) | ||||
| Prokinetic Medications | 6/14 (42.9%) | 8/18 (44.4%) | 403/939 (42.9%) | >0.99 |
| Gastric Electrical Stimulator | 5/14 (35.7%) | 8/18 (44.4%) | 55/939 (5.9%) | < 0.001 |
| Narcotic Use | 10/14 (71.4%) | 7/18 (38.9%) | 295/939 (31.4%) | 0.006 |
| Hospitalizations – no. (%) | ||||
| Hospitalized in Past Year | 13/14 (92.9%) | 14/18 (77.8%) | 356/939 (37.9%) | < 0.001 |
P values for Fisher’s exact test for comparison of categorical variables, Kruskal-Wallis tests for comparison of medians for highly skewed distributions, and ANOVA for comparison of means. All values are medians (Q1,Q3) unless noted otherwise.
Waist to hip ratio health risk is reported as low (waist circumference ≤0.80 for women and ≤0.95 for men), medium (0.81 - 0.85 for women and 0.96-1.0 for men), and high (≥0.86 for women and >1.0 for men).
The TPN and EN patients were younger (mean=36, 38 vs 44 years; p=0.03), had lower BMI (mean=24, 24 vs 28; p=0.01), smaller waist circumference (82.9, 83.4, 92.1 cm; p=0.04), and had more severe symptoms with higher nausea/vomiting subscore (median=3.5, 3.2 vs 2.3; p=0.04), early satiety/postprandial fullness subscore (median=4.1, 4.3 vs 2.3; p=0.04), upper and lower abdominal pain scores compared to ON patients (Table 1). Patients on TPN or EN had 8 point lower SF-36 physical QOL, whereas mental QOL scores were similar across groups. TPN and EN patients ingested less water during the WLST (mean=169, 216 vs 394 mL; p=0.007), but did not have worse gastric emptying compared to ON patients. In the year prior to enrollment, 93% of the TPN patients and 78% of EN patients had hospitalizations, compared to only 38% of ON patients (p<0.01). In addition, 93% of TPN patients were idiopathic etiology and almost 20% more had an acute onset (64% vs 44%, 43%) compared to EN or ON. All groups were similar for severity of depression though more TPN patients had moderate to severe anxiety (79% vs 61% vs 56%), though not significant.
48 week follow up
There was 48 week follow up on 554 (57%) of the gastroparesis patients in this study (Table 2). Of 536 ON patients at enrollment, 8 (1.5%) required EN, and 7 (1.3%) required TPN over the 48 weeks. Of 10 TPN patients at enrollment, 5 (50%) remained on TPN and 5 (50%) resumed ON. Of 8 EN patients at enrollment, 5 (63%) remained on EN, 1 (12%) required TPN, and 2 (25%) resumed ON. Patients receiving TPN or EN were more likely to be receiving gastric electric stimulation therapy both at baseline and at 48 weeks (29% vs 7%; 55% vs 6%, respectively).
Table 2.
Nutritional Sources: Enrollment and 48 weeks (for patients seen at both enrollment and at 48 weeks)
| NUTRITION AT ENROLLMENT | |||
|---|---|---|---|
| Oral | Enteral | Parenteral | |
| N = 536 | N = 8 | N = 10 | |
| NUTRITION at 48 WEEKS | |||
| Oral Feedings Only | 521 (97.2%) | 2 (25.0%) | 5 (50.0%) |
| Enteral Nutrition | 8 (1.5%) | 5 (62.5%) | 0 (0%) |
| Parenteral Nutrition | 7 (1.3%) | 1 (12.5%) | 5 (50.0%) |
Among those on ON at baseline, we looked for factors associated with needing TPN/EN over the 48 weeks. We compared the 15 ON patients at enrollment that required EN and/or TPN at 48 weeks to the 521 ON patients at enrollment that remained on ON (Supplemental Table 1). At baseline, the 15 patients needing EN/TPN at 48 weeks had significantly lower body mass index (median 20.4 vs 27.6; p<0.001), smaller waist circumference (73.1 vs 93.1; p<0.01), smaller waist to hip ratio (0.81 vs 0.88; P<0.001), lower SF-36 PCS (median 23.1 vs 33.1; p=0.01), and higher lower abdominal pain score (median 3.5 vs 2.5; p=0.06). At the 48 week visit, the 15 ON patients requiring TPN/EN had higher early satiety subscore (3.8 vs 3.0; p=0.013), GCSI score (3.1 vs 2.8; p=0.05), upper abdominal pain score (3.5 vs 2.5; p=0.05), and lower abdominal score (3.5 vs 2.0; p=0.007). The ON patients progressing to TPN had significantly lower PAGI-QOL overall score at 48 weeks than the ON patients staying on ON (1.6 vs 2.9; p=0.002). The ON patients progressing to TPN/EN received more new treatments for their gastroparesis in the form of gastric electric stimulation, domperidone, or abdominal surgery (47% vs 19%; p=0.02). The ON patients progressing to TPN had declines in their QOL from baseline to 48 weeks (SF-36 PCS of −1.2, SF-36 MCS of −1.8, and PAGI-QOL overall of −0.77), whereas the patients staying on ON had small increases in these scores.
We also looked for factors associated with coming off TPN/EN to ON for the 7 (39%) TPN/EN patients during the 48 weeks follow-up by comparing these patients to the 11 TPN/EN patients who remained on TPN/EN at the 48 week follow up (Supplemental Table 2). At baseline, the patients coming off TPN/EN had higher nausea/vomiting subscore (median 4.7 vs 2.7; p=0.04), GCSI score (median 4.1 vs 3.1; p=0.04). At 48 weeks, the patients coming off TPN/EN and resuming ON had higher bloating subscore (median 4.0 vs 2.5; p=0.09) and GCSI score (median 4.0 vs 2.8; p=0.10). On average, patients coming off TPN/EN to ON gained weight over 48 weeks compared to patients staying on TPN who lost weight (+2.5 vs −1.4; p=0.06).
Comparison of Patients using PN and/or EN to ON Patients never on TPN/EN
To capture all patients receiving TPN and EN in the registry over their 48 week enrollment, we looked at not only the 32 patients receiving TPN/EN at enrollment, but also the 15 patients who were on ON at enrollment that required TPN/EN by 48 weeks, providing 47 patients (4.8%) using nonoral nutrition during the 48 weeks (Table 3). We compared these 47 TPN/EN patients to 924 patients that never received TPN/EN (on ON at baseline and at 48 weeks). Patients requiring supplemental nutrition (TPN and/or EN) were generally 7 years younger and had lower BMI by 6 kg/m2 than ON patients. TPN/EN patients were more symptomatic with higher nausea subscores, early satiety subscores, upper abdominal pain subscores, GERD scores, and overall GCSI. The TPN/EN patients had lower QOL, both in the SF-36 PC and PAGI-QOL, but not the SF-36 MC. TPN/EN patients at any visit as a group had more severe delayed (i.e., >35% retention at 4 hours) gastric emptying (51% vs 36%; p=0.06). In addition, these patients had significantly reduced water volume ingested during the WLST (180 vs 355 mL; p<0.001). Patients receiving nutritional support were more likely to use domperidone, have a gastric stimulator and use narcotic medications supporting that they were more symptomatic.
Table 3.
Comparison of Patients who were on TPN/EN (at baseline or 48 weeks) to Patients Never on TPN
| On TPN/EN | Never on TPN/EN | P† | |
|---|---|---|---|
| N | 47 (4.8%) | 924 (95.2%) | |
| Characteristics at Visit | |||
| Etiology | 35 IGp, 12 DGp | 544 IGp, 324 DGp, 51 PFGp | 0.12 |
| Age | 38.4 (19, 63) | 45 (18, 84) | 0.002 |
| Female Sex | 43 (92%) | 774 (84%) | 0.22 |
| BMI | 21.0 (18.6, 24.2) | 27.1 (22.1, 32.6) | <0.001 |
| Waist Circumference (cm) – mean (SD) | 80.0 (15.7) | 92.4 (19.1) | <0.001 |
| Waist-To-Hip Ratio – mean (SD) | 0.87 (0.11) | 0.89 (0.09) | 0.18 |
| Waist-To-Hip Ratio Health Risk – no. (%) | |||
| Low | 14 (29.8%) | 216 (23.4%) | 0.02 |
| Moderate | 15 (31.9%) | 177 (19.2%) | |
| High | 18 (38.3%) | 530 (57.4%) | |
| Nausea subscore | 3.3 (2.2, 4.2) | 2.0 (1.0, 3.3) | <0.001 |
| Early satiety subscore | 4.0 (3.3, 4.5) | 3.3 (2.5, 4.0) | <0.001 |
| Bloating subscore | 3.0 (2.0, 4.5) | 3.0 (2.0, 4.0) | 0.77 |
| GCSI Score | 3.2 (2.8, 4.0) | 2.9 (2.0, 3.5) | 0.001 |
| Upper abdominal pain | 4.0 (3.0, 4.6) | 3.0 (1.5, 4.0) | <0.001 |
| GERD Score | 2.6 (1.6, 3.2) | 1.7 (0.8, 2.9) | 0.002 |
| SF-36 PCS | 26.6 (19.3, 31.2) | 33.4 (26.1, 41.9) | <0.001 |
| SF-36 MCS | 37.0 (26.8, 48.4) | 40.5 (29.9, 51.8) | 0.34 |
| PAGI-QOL overall score | 1.9 (1.0, 2.8) | 2.8 (1.9, 3.6) | <0.001 |
| Gastric retention 4 hrs (%) | 36 (20, 51) | 26 (17, 45) | 0.06 |
| Severe Retention (4 hr R > 35%) | 23/45 (51.1%) | 332/916 (36.2%) | 0.06 |
| Volume Water WLST (ml) | 180 (100, 330) | 355 (237, 500) | <0.001 |
| Hospitalized in past year (%) | 31/47 (66.0%) | 229/923 (24.8%) | <0.001 |
| Prokinetic Use | 21/47 (44.7%) | 318/924 (34.4%) | 0.16 |
| Domperidone Use | 10/47 (21.3%) | 109/924 (11.8%) | 0.07 |
| Gastric stimulator | 13/47 (27.7%) | 89/924 (9.6%) | <0.001 |
| Narcotic Use | 25/47 (53.2%) | 321/924 (34.7%) | 0.01 |
NOTE: Values reported are median (Q1, Q3) or N (%) unless otherwise noted. Values shown correspond to the patient’s most recent visit, except for patients on TPN/EN at baseline and not 48 weeks, where values shown are from the baseline visit.
Waist to hip ratio health risk is reported as low (waist circumference ≤0.80 for women and ≤0.95 for men), medium (0.81 - 0.85 for women and 0.96-1.0 for men), and high (≥0.86 for women and >1.0 for men).
P values for Fisher’s exact test for differences in categorical measures or Wilcoxon rank sum tests or t tests for differences in continuous measures
We performed a multivariable analysis to describe the characteristics of patients that were using TPN/EN. Candidate factors analyzed included acute vs. insidious symptom onset, BMI, number of hospitalizations in prior year, PAGI-QOL overall score, narcotic use, gastric retention at 4 hours, nausea/vomiting subscore, bloating subscore, early satiety/postprandial distension subscore, and upper abdominal scores. The stepwise algorithm identified a multivariable model demonstrating that lower BMI (OR=0.87, CI=0.81, 0.93; p<0.001), higher nausea/vomiting subscore (OR=1.59, CI=1.20, 2.08; p=0.001), higher early satiety/postprandial distension subscore (OR=1.79, CI=1.16, CI=2.75; p=0.008), and use of narcotic analgesia (OR=2.33, CI: 1.15, 4.69; p=0.02) were independent factors associated with use of TPN/EN (Table 4).
Table 4.
Multivariable model for association between patient characteristics and use of TPN/EN at either baseline and/or 48 weeks.
| Odds Ratio† [95% CI] | P | |
|---|---|---|
| BMI (per 1 kg/m2 unit) | 0.87 [0.81, 0.93] | < 0.001 |
| Early Satiety Score (per 1 point) | 1.79 [1.16, 2.75] | 0.008 |
| Nausea (per 1 point) | 1.58 [1.20, 2.08] | 0.001 |
| Bloating (per 1 point) | 0.76 [0.59, 0.98] | 0.03 |
| Narcotic use (yes v no) | 2.33 [1.15, 4.69] | 0.02 |
A total of 837 patients were included in the model, with 38 (4.5%) having ever been on TPN/EN and 799 (95.5%) not. The final model shown was selected using a forward and backward stepwise selection approach with a minimum AIC for selection criteria.
Candidate factors analyzed included acute vs. insidious symptom onset, BMI, number of hospitalizations in prior year, PAGI-QOL overall score, narcotic use, gastric retention at 4 hours, nausea/vomiting subscore, bloating subscore, early satiety/postprandial distension subscore, and upper abdominal scores.
NOTE: CI = Confidence Interval
Odds ratios from a multivariable logistic regression model with use of TPN/EN as the dependent variable and all characteristics shown in the table as independent variables.
Discussion
This study describes the frequency and characteristics of gastroparesis patients requiring chronic TPN and/or EN for nutritional support. These patients represent a small (3.3%), but important, subset of patients with gastroparesis enrolled in our NIDDK Gastroparesis Registry. We found that nutritional support use with either EN or TPN was associated with greater severity of gastroparesis symptoms and poorer physical quality of life than ON patients. Over 48 weeks of follow up, half or fewer of these patients resumed oral feedings for nutrition: 50% of patients on TPN and 25% of patients on EN. Of 536 Gp patients using ON at enrollment with follow-up data, 2.8% worsened to need EN or TPN over 48 weeks follow-up.
The incidence of gastroparesis patients needing EN or TPN is not well known; most studies are retrospective reports. In the 1998 series of McCallum et al, 21% of the 146 patients seen over 6 years at some point required nutrition support with a feeding jejunostomy tube or periods of parenteral nutrition (17). Our study found that a small (3.3%) percentage of patients enrolling in our registry required EN or TPN, with the number of patients on enteral nutrition outnumbering those on parenteral nutrition (1.9% using EN, 1.4% using TPN). Over the 48 week time period, an additional 2.7% of patients needed TPN/EN.
Patients who were on EN or TPN were more symptomatic with lower BMI than patients receiving ON, suggesting, as may be expected, that symptoms and nutritional status play important roles in the clinical decision on whether to use and continue EN/TPN. This was true for patients at both baseline and 48 weeks who were on TPN/EN. Prior studies have shown that patients with gastroparesis have a decreased physical QOL with preserved mental QOL (18,19). This study expands on these findings in demonstrating that the gastroparesis patients on EN and TPN have a poorer physical quality of life than the many gastroparesis patients on ON. The presence of increased symptoms, feeding tubes/catheters, the time needed to prepare and infuse nutrients, and the ongoing care of the tubes/catheters may contribute to these poorer physical QOL scores. The increased symptom severity may have led to the increased usage of domperidone, opiates, and gastric electric stimulation seen in those with TPN/EN.
Our study also explored 48 week follow up period of patients. We found that half or fewer of the patients on EN or TPN on enrollment were able to come off this nutritional support and resume oral feedings for nutrition: 50% of patients on TPN and 25% of patients on EN. Thus, the decision to proceed with EN or TPN, both of which can be temporary, is often continued for a long time. On the other hand, going onto EN or TPN is not irreversible. 50% of patients on TPN and 25% of patients on EN were able to go back to oral intake over 48 weeks. Interestingly, patients who came off TPN/EN were sicker at baseline compared to patients who stayed on TPN/EN, with significantly higher baseline nausea/vomiting severity and overall gastroparesis severity. At 48 weeks, patients coming off TPN/EN had significantly higher bloating severity and overall gastroparesis severity, possibly from consuming ON at 48 weeks or because this group of patients had higher severity that was maintained from baseline. The TPN/EN patients coming off TPN/EN had numerically more new treatments than those remaining on TPN/EN, implying that ongoing treatment may help patient resume ON. Patients receiving TPN/EN were more likely to be receiving gastric electric stimulation therapy both at baseline and at 48 weeks, which could reflect significantly worse symptoms severity among this population. Gastric electrical stimulation implantation has been shown to improve nutritional parameters (20), but whether this relationship is true in our sample is unknown.
TPN/EN Gp patients had more gastric physiologic dysfunction as evidence by the significant decrease in volume of water able to be consumed during the WLST. This may be part of the reason the patients are needing supplemental nutrition as enough liquid/solids are not being ingested. By looking at the patients that required TPN/EN over the 48 weeks, we were able to better understand the independent factors leading to use of TPN using a multivariable analysis. Patients that required TPN in our NIDDK Gastroparesis Registry Studies had lower BMI with higher nausea and early satiety scores and were often taking narcotic analgesia presumably for abdominal pain.
There are some limitations to this study. Our registry was designed to look at patients with gastroparesis and treatments. This descriptive cohort study is an exploratory hypothesis generating study. Due to the small numbers of subjects in the EN and TPN groups, any inferences are limited by low power and have an increased risk of false-positive findings. The information presented is limited to patients seen at the specialized gastroparesis centers involved and willing to enter the registry study. It may have had the potential to miss the sickest patients who are not willing to enter the study, and who are most likely higher users of enteral and parenteral support. The registry did not capture why the patient had to start EN or TPN, and exactly when this nutrient delivery was started. The registry also did not record complications of treatment with EN or TPN. Prospective research is needed with focused cohorts of larger number of patients who are being placed on EN/TPN. Nevertheless, the primary strengths of the study lie in its ability to use a national multicenter database to compare those with gastroparesis placed on EN/TPN vs. those without using validated questionnaires and standardized follow-up intervals. As a registry, the study also captures standard clinical practice across the United States, increasing the generalizability of the findings.
In summary, this study describes Gp patients requiring chronic TPN and/or EN for nutritional support: a small but important subset of patients with Gp. In our series, they represent 3.3% of our gastroparesis patients at enrollment. Those with Gp requiring TPN/EN are more symptomatic with low volumes of water ingestion and have a poorer physical quality of life than ON patients associated with increasing therapies. Over 48 weeks, half or fewer of these patients resumed oral feedings for nutrition. Of Gp patients using ON at enrollment, 2.7% worsened to need EN or TPN over 48 weeks follow up. A multivariable model demonstrated that patients with lower BMI reporting higher nausea and early satiety subscores often taking narcotics were more likely to be on TPN/EN. Thus, this study provides valuable information on this important symptomatic subgroup of patients with gastroparesis. This study will hopefully encourage future research to help reduce chronic use of EN/TPN in patients with gastroparesis.
Supplementary Material
Funding:
The NIH/NIDDK Gastroparesis Clinical Research Consortium (GpCRC) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK073975 [Parkman], U01DK073983 [Pasricha], U01DK074007 [Abell], U01DK073974 [Koch], U01DK074035 [McCallum], U01DK112193 [Kuo], U01DK074008 [Tonascia]). This manuscript was also supported by K23DK131334 (Burton Murray).
Footnotes
ClinicalTrials.gov Identifier: NCT01696747
Competing Interests: the authors have no competing interests.
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