Using Polyethylene Glycol 3350 Plus Electrolytes In Constipated Hemodialysis Patients: A Case Series Ⅱ
Sep 28, 2023
Participants
Among 66 patients on in-center hemodialysis in our hospital, 12 were dependent on stimulant laxatives for controlling functional constipation, which was diagnosed according to the Rome III criteria (10). Nine of the 12 patients agreed to participate, and 7 completed this study; their characteristics are summarized in Table 1. All patients had been receiving dialysis for more than 10 years. Stimulant laxatives included sennoside, nonprescription drugs containing sennna, and herbal medicines containing rhubarb.
The dose of stimulant laxatives just before the intervention was expressed as a low or high dose compared with the upper limit of the recommended dose. All patients had been examined by colonoscopy within the preceding three years to confirm that their constipation was not caused by organic diseases. Pseudomelanosis coli was observed in six patients, which may reflect long-term continuous use of stimulant laxatives.
There were 3 phases in total during the 10-week study period (Fig. 1). The first two weeks were pre-intervention periods to serve as a baseline. During the pre-intervention periods, patients took laxatives, including stimulant laxatives that had been used before this study.
After the preintervention period, participants were treated with PEG3350 +E for six weeks (intervention period). PEG3350+E is a minimally absorbable iso-osmotic agent with a high molecular weight (11). It is a powder formulation delivered in sachets, each containing 6.5625 g of PEG, 0.1754 g of sodium chloride, 0.0893 g of sodium bicarbonate, and 0.0251 g of potassium chloride. One sachet was dissolved in 62.5 mL of water.
Since there was no evidence concerning the safety of PEG3350+E in hemodialysis patients, PEG3350+E was administered starting at the minimum dose. Initially, one sachet of PEG3350+E per day was administered in the first week of the intervention period, and then patients were allowed to take an additional sachet each week. Patients were allowed to take a maximum of six sachets of PEG3350+E per day in the final week of the intervention period.
During the intervention period, patients were carefully observed in case they developed any adverse events. The amount of PEG 3350+E was adjusted to reduce stimulant laxatives and increase SBMs with the ideal stool consistency during the intervention period. The last two weeks were a postintervention period for comparison with the baseline. The amounts of PEG3350+E and stimulant laxatives were fixed during the post-intervention period. Any changes in medications for hyperphosphatemia that might affect the control of constipation were allowed throughout the study.
Under the assumption of a Gaussian distribution, the measured variables are expressed as the mean standard deviation. To evaluate the efficacy, a nonparametric Wilcoxon’s signed rank test was used to avoid the influence of outliers. In the safety analyses, variables were measured in nested format (three measurements per week in a patient, repeated for several weeks) so that we applied the random effect multilevel linear regression model. Two-sided p<0.05 was regarded as statistically significant. Statistical analyses were performed using the software program Stata ver. 13.1 (StataCorp LLC, College Station, USA) and Excel 2013 (Social Survey Research Information, Tokyo, Japan).
This observational study was conducted between May and August 2019, and it was performed by the ethical principles established in the Declaration of Helsinki and Good Clinical Practice guidelines. The protocol and informed consent form were approved by the ethics committee in our hospital. Although this was not an interventional study, patients were informed about the study via a document and agreed to participate by signing the informed consent form. Patients were allowed to drop out for any reason, and the safety of the patients received close attention throughout this study.
During this study, patients recorded all of their bowel movements (BMs) and uses of stimulant laxatives with a paper diary. To assess BMs, the sensation of incomplete evacuation and severity of straining were scored as follows: absent=0, present=1. Stool consistency was scored using the Bristol Stool Form Scale (BSFS) (12).
The patients’ quality of life (QOL) with constipation was assessed in the final pre-intervention and post-intervention periods, based on the Japanese version of the Patient Assessment of Constipation Quality of Life Questionnaire (JPAC-QOL) (13). SBMs were defined as bowel movements without the use of a stimulant laxative, suppository, or enema in the preceding 24 hours. Complete SBMs (CSBMs) were defined as SBMs associated with a sense of complete evacuation. We evaluated a BSFS of 4 or 5 as the ideal stool consistency according to the recent reports in Eastern cohorts (14, 15).
The ratios of SBMs, CSBMs, and BMs with ideal stool consistency and no straining to total BMs were calculated in the pre- and postintervention periods. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the beginning of every dialysis session (three times a week). Weight gain between every dialysis session was calculated based on the data of body weight at the beginning and end of every dialysis session (three times a week). The serum levels of sodium, potassium, and albumin were monitored every week (once a week).
The amount of sodium chloride intake was estimated using the serum sodium levels before and after the dialysis session according to the previous report (once a week) (16). These parameters were monitored throughout this study. The mean of SBP, DBP, weight gain, data from serum samples, and sodium chloride intake were calculated every two weeks. The reduction or discontinuation of PEG3350+E was considered in any of the following cases: development of hypertension that required additional medications, body weight gain more than 1 kg compared to that average of the previous week, elevation of serum sodium concentration over 5 mEq/L and elevation of serum potassium concentration over 2 mEq/L compared to the previous week.
The amount of stimulant laxatives and PEG3350+E in the post-treatment periods and medications for hyperphosphatemia are summarized in Table 2. No stimulant laxatives were necessary in four of the seven patients (responders: Case 1, 2, 5, and 6). The remaining three patients (partial responders: Cases 3, 4, and 7) achieved a reduction in the dose of stimulant laxatives. The medications for hyperphosphatemia did not change, except for one case (Case 7) where the dose of lanthanum carbonate for hyperphosphatemia was increased during the intervention period.
The parameters concerning the efficacy are summarized in Table 3 and Fig. 2. By taking PEG3350+E, the average amount of stimulant laxatives decreased dramatically to 25.8% of the baseline (Fig. 2A, 2B). The ratio of SBMs and CSBMs to total BMs increased significantly in the posttreatment period compared to the baseline. As shown in Fig. 2C and D, BMs gradually improved during the six-week intervention period.
The ratio of BMs with ideal stool consistency to total BMs was significantly higher during the posttreatment period than at the baseline, although there was no significant change in the ratio of BMs with no straining. The JPAC-QOL was significantly lower during the post-treatment period than at the baseline, indicating an improvement in the QOL concerning constipation.
The parameters for assessing PEG3350+E safety are summarized in Table 4. Patients took 2 or 4 sachets of PEG+E per day, which contained 13.125-26.25 g of PEG, 0.35-0.7 g of sodium chloride, and 0.05-0.10 g of potassium chloride. The amount of water needed for the dissolution of PEG3350 +E was 125-250 mL per day.
Despite electrolyte and water loading, there were no significant changes in the sodium chloride intake or body weight gain throughout the study. The serum levels of sodium, potassium, and albumin showed no significant changes between pre-and post-intervention. The SBP did not show a significant difference before and after the intervention, although the DBP significantly increased after the intervention.
Natural Herbal Medicine For Relieving Constipation-Cistanche
Cistanche is a genus of parasitic plants that belongs to the family Orobanchaceae. These plants are known for their medicinal properties and have been used in Traditional Chinese Medicine (TCM) for centuries. Cistanche species are predominantly found in arid and desert regions of China, Mongolia, and other parts of Central Asia. Cistanche plants are characterized by their fleshy, yellowish stems and are highly valued for their potential health benefits. In TCM, Cistanche is believed to have tonic properties and is commonly used to nourish the kidney, enhance vitality, and support sexual function. It is also used to address issues related to aging, fatigue, and overall well-being. While Cistanche has a long history of use in traditional medicine, scientific research on its efficacy and safety is ongoing and limited. However, it is known to contain various bioactive compounds such as phenylethanoid glycosides, iridoids, lignans, and polysaccharides, which may contribute to its medicinal effects.
Wecistanche's cistanche powder, cistanche tablets, cistanche capsules, and other products are developed using desert cistanche as raw materials, all of which have a good effect on relieving constipation. The specific mechanism is as follows: Cistanche is believed to have potential benefits for relieving constipation based on its traditional use and certain compounds it contains. While scientific research specifically on Cistanche's effect on constipation is limited, it is thought to have multiple mechanisms that may contribute to its potential to relieve constipation. Laxative Effect: Cistanche has long been used in Traditional Chinese Medicine as a remedy for constipation. It is believed to have a mild laxative effect, which can help promote bowel movements and induce constipation. This effect may be attributed to various compounds found in Cistanche, such as phenylethanoid glycosides and polysaccharides. Moistening the Intestines: Based on traditional use, Cistanche is considered to have moisturizing properties, specifically targeting the Intestines. Promoting hydration and lubrication of the Intestines, it may help soften tools and facilitate easier passage, thereby relieving constipation. Anti-inflammatory Effect: Constipation can sometimes be associated with inflammation in the digestive tract. Cistanche contains certain compounds, including phenylethanoid glycosides and lignans, that are believed to have anti-inflammatory properties. By reducing inflammation in the intestines, it may help improve bowel movement regularity and relieve constipation.
