.182 .Chiness Joumal of Traumatology 2010; 13)3):182-187Efficacy of polyethylene glycol 4000 on constipation ofposttraumatic bedridden patientsZHANG Lian-yang張連陽*, YAO Yuan-zhang姚元章, WANG Tao王韜FEI Jun費軍, SHEN Yue沈岳CHENYong-hua 陳永華and ZONG Zhao-wen宗兆文[Abstract] Objective: To investigate the eficacyfor two weeks, patients with slight movement showed aand safety of polyethylene glycol 4000 (Forlax*) on adultsignificantly higher remission rate than those without move-patients with functional constipation due to posttraumaticment (95% Vs 80%). At the end of treatment, most accompa-confinement to bed.nying symptoms were relieved obviously. Patients with aMethods: A total of 201 psttaumatic bedridden pa-medical history of constipation or ever taking laxativestients were studied in this prospective, open-labeled, single-showed a lower remission rate. Sixty cases (29.85%) devel-group study. Polyethylene glycol 4000 was administeredoped diarrhea during the observational period, among whomorally for 14 days and the dosage was adjusted according6 (10%) withdrew from the clinical observation voluntarilyto the Bristol stool types. Demographic characteristics, dis-at the first onset of diarrhea. Two cases suffered from ab-ease status, treatment period and factors affecting clinicaldominal pain.outcome, especially the concomitant medications, wereConclusions: Polyethylene glycol 4000 (Forlax*) hasrecorded.efficacy on functional constipation in posttraumatic bed-Results: After administration of polyethylene glycolridden patients. Furthermore, patients with milder symptoms,4000, 194 cases (96.52%) showed remission of constipation,more movement in bed, and longer duration of treatmentincluding 153 (76. 12%) persistent remission. The averagebut without accompanying symptoms can achieve a higherdefecation frequency increased significantly after treatmentremission rate.and the percentage of patients with stools of normal typesKey words:Polyethylene glycols; Wounds and(Bristol types 3-5) increased as well. Genders, ages and con-injuries; Bed rest; Constipation; Therapeuticscomitant medications showed no significant influence onthe persistent remission rate. After consecutive treatmentChin J Traumatol 2010; 13)3):182-187onstipation is one of the most common chronicIrritants or lubricants can relieve the symptoms, butgastrointestinal problems. The estimated in-long-term application of them may lead to side effectscidence of constipation in the United Stateslike melanosis colifs and cathartic colon6. The absorp-is 3% to 19% in general population.12 Patients with headtion of fat soluble vitamins is also afected." PolyethyI-injuries, spinal cord injuries, pelvic fractures, lower ex-ene glycol 4000 (trade name: Forlax), a long chaintremity fractures or multiple traumas require a long-termpolymer with a high molecular weight, can conjugatebed rest, during which the incidence of constipationwith water molecule through hydrogen bond to increasereached as high as 50%.4 Constipation always bringsthe water content and volume of stools, thereby, faciliinconvenience and tremendous suffering to patients andtate bowel movement and defecation.8.9 It is neither ab-strongly infuences the recovery from primary disease.sorbed nor metabolized in the digestive tract, hence itis highly safe and well tolerable. Thus, long-term medi-cation of polyethylene glycol 4000 is conducive to theDOI: 10.3760/cma.j.issn. 1008-1275 2010.03.010State Key Laboratory of Trauma, Burns and Combinedreconstruction of normal defecation patterm. Therefore,Injury, Trauma Center of PLA, Institute of Surgery Research,polyethylene glycol 4000 is now being widely used as theDaping Hospital, Third Military Medical University,中國煤化工nal constipationChongqing 400042, China (Zhang LY, Yao YZ, Wang T, Feimanajdy was to verify theJ, Shen Y, Chen YH and Zong ZW)efficH, CNM H Gycol 4000 on adut*Corresponding author: Tel: 86-23-68757991, E-mail:functional constipation of posttraumatic bedriddenhpzhangly@163.compatients.Chinese Joumal of Traumatloy 2010; 13/3):182-187.183.METHODSdysfunctions; (3) having abdominal surgeries in recent6 months; (4) alergic to polyethylene glycol 4000; (5)Patientswith organic intestinal diseases such as colorectalA total of 201 posttraumatic patients in bed resttumor, infammatory bowel disease, polypus, diverti-admitted to the Department of Traumatic Surgery, Reculum, hypogenesis or malformation identified by his-search Institute of Surgery, Daping Hospital, Third Mili-tory of present ilness, physical examination or othertary Medical University between May 2007 and Sep-examinations; and (6) taking other laxatives.tember 2008, who received the treatment of polyethy-ene glycol 4000, were included in this prospective, open-Drug and dosagelabeled, single-group, single-center study. There werePolyethylene glycol 4000 (Forlax", 10 g/sachet)143 males (71. 14%) and 58 females (28.86%), agedmanufactured by Beaufour Ipsen Industrie (Dreux,18-75 years including 141 younger than 50 years, meanFrance) was given orally for 14 consecutive days and43.29 years. Among them, 24 (11.94%) had a historythe dosage was adjusted according to the Bristol stoolof constipation and 9 (4.48%) had ever received laxa-classification as fllows: (1) Bristol types 1-2, 20 g fortives for treating constipation. Of the 201 posttraumatic4 times a day; (2) Bristol types 3-5, 10 g for 4 times abedriden patients, 104 had lower extremity fractures,day; (3) Bristol types 6-7, discontinuation of treatment55 spinal fractures (including 4 with paraplegia), 13for 24 hours; and (4) those with no defecations in thepelvic fractures and 29 chest or head injuries. Amongpast 24 hours, continuation of treatment with the samethe 104 patients with lower extremity fractures, 100 haddosage as the previous day.received internal or external fixation surgeries and 4had taken plaster external fixation. Totally, there wereEndpoints of the treatment were: (1) completion of140cases (69.65%)unabletomove voluntarily, 61 (30.35%)the 14-day treatment, or (2) more than 3 times of de-able tomove slighty ontheir beds, and 123 (61.19%)hav-fecation per day for consecutive 2 days or sools of Bristoling taken drugs likely to cause constipation during thetypes 6-7.bedridden peniod. During one week before treatment, 98patients (48.76%)had one defecation, 63(31.34%)twice,Outcome assessment22 (10.95%) three times and 18 (8.96%) more than threeRecruitment and completion status, demographictimes. Stools of all patients were classified into Bristoldata, disease conditions, treatment duration, achieve-types 1-4 and the patients' number of each type wasment of the endpoint or not, and slight movement in91 (45.27%), 53 (26.37%), 40 (19.90%)and 17 (8.46%).bed or not were all documented. Concomitant medica-tions were also recorded accurately, especially thoseInclusion and exclusion criterialikely to cause constipation, such as opioid analgesics,Witen informned consents of patients were obtainedantipsychotic drugs, anticonvulsants, calcium channeland documented before their participation in the trial.blockers, anticholinergics, dopamine analogues and bilePatients were included in this trial according to the fol-salts binders.lowing criteria: (1) age between 18 and 75 years ire-spective of genders; (2) being bedridden and unable toThere are three main indexes in this study to evalu-defecate on bedside or toilet for more than 1 week; (3)ate the therapeutic effects of polyethylene glycol 4000.having returmed to a normal diet for at least 5 days; (4)(1) Constipation remission, which was described by thewith an expected bed-ridden duration more than 2remission and persistent remission rate, remissionweeks; and (5) having presented with at least one ofduration, time of the first remission, and restoration ofthe symptoms for more than 3 days (hard and lumpynormal defecation pattern. The proportion of patientsstools in Bristol types 1-2, hand-assisted defecation, noachieved constipation remission for more than 3 daysdefecation in consecutive 3 days or less than 3 timeswith 1-2 times of defecation/day and stools of Bristolof defecation in the past week).types中國煤化工ent remission ratesof palCNMH(Fes 1-2, less than3Patients were excluded from this trial if they mettimes Un uoiocauowweon UCIUIC ueatment and hand-any of the fllowing criteria: (1) nothing by mouth (NPO)assisted defecation at the first day of treatment werepatients; (2) with dysphagia, severe hepatic or renal calculated. We comparied the persistent remission rates。184.Chinese Joumel of Traunatology 2010; 13):182-187among patients with different ages, genders, concomi-After the administration of polyethylene glycol 4000,tant medications and accompanying symptoms at dif-194 patients (96.52%) showed a constipation remission.ferent time points. (2)Accompanying symptoms, whichThe first remission occurred (3.65+2.22) days after treat-were described by incidence of accompanying symp-ment and 153 cases (76. 12%) achieved a persistenttoms at the beginning of treatment and the end of theremission. Patients with less than 3 times of defeca-first or second weeks. And (3) adverse effects such astion in one week before treatment had a remission ratediarrhea and abdominal pain. The conditions of diar-of 74.86%. Patients with Bristol stool types 1-2 andrhea were also described, including the onsetof dianhea,hand-assisted defecation showed a remission rate ofwithdrawl from the observation due to diarhea, and di-72.92% and 100%, respectively. Seventy-five casesarthea when withdrawing from the study. Persistent(37.31%) restored a normal defecation pattern afterRemission was defined as 1-2 times of defecation perdiscontinuation of the drug. Only 7 cases (3.48%)day with Bristol type≥3 in 3 consecutive days duringshowed no improvement at all. The bowel movementsthe 14-day treatment period.increased significantly after treatment (Figure 1). Thepercentage for patients with stools of Bristol types 1-2Statistical analysisdecreased significantly, while that for patients with stoolsAll subjects were included in a full analysis setof Bristol types 3-5 increased (Figure 2). The persis-(FAS). Descriptions of the numerical variables includedtent remission rate was 45.71% for patients taking medi-sample size, mean, standard deviation, median, maxi-cations for less than one week, and 85.04% for thosemum and minimum values. And descriptions of categori-taking medications for 2 weeks. Genders ( x2=0.46,cal variables included the number and percentage ofP=0.4992), ages ( x 2=0.93, P=0.3341) and concomi-cases flling into various categories. The statisticaltant medications ( x2=0.22, P=0.6411) showed no con-analysis was bilateral and data were recognized statis-siderable impact on the persistent remission rate. Aftertically significant when P<0.05. By means of cochran-two weeks of consecutive treatment, the remission rateMantel-Haenszel (CMH) test, comparison was per-was 95.00% for patients who could move slightly onformed on the persistent remission rates of differentthe bed, and 80.46% for those unable to move (Table 1).genders. The same method was also used to compareThe remission rate was 78.95% for patients who hadthe persistent remission rates of patients with differentreached the treatment endpoint, while 60.00% for thoseages, Bristol types before medication, history of con-failed ( x2=5.04, P=0.0248, Table 2).stipation and laxative medications, concomitant medi-cations and accompanying symptoms respectively,Concomitant symptoms of constipationalso the eficacy of polyethylene glycol 4000 and medi-In this study, 36 cases (17.91%) had accompany-cation for subsequent treatment.ing symptoms before treatment, inluding 22 (10.95%)with abdominal pain, 13 (6.47%)with dffcult defecation,RESULTS6 (2.99%) with anorexia and 1 (0.50%) with hand-as-sisted defecation. At the end of treatment, most symp-Efficacytoms were relieved significantly, with a 100% remis-Totally, 171 cases (85.07%) fnally reached the treat-sion rate in patients with difcult defecation or anorexia.ment endpoint, among whom 127 (63. 18%) receivedBut the hand-assisted defecation and abdominal painthe polyethylene glycol 4000 treatment for 14 days andin 3 cases (1.49%) remained.the rest (44 cases) had more than 3 times of defeca-tion in 2 consecutive days or with stools of Bristol typesAdverse effects6-7. The other 30 cases (14.93%) failed to reach theTotally, 60 patients (29. 85%) developed diarthea,treatment endpoint due to various reasons. The meanamong whom 6 (10%) withdrew from the clinical obser-duration of polyethylene glycol 4000 therapy was (11.81 .vation at the first onset of diarhea, and 43 (71.67%)+3.26) days. In this clinical observation, 35 patiens with-staye中國煤化工complained of ab-drew in the first week and 39 in the second week.domiCNM H Gne elieved sponta-neously anu ue uuner rulievou aler drug discontinuation.Chinese Joumal of Traumatoloy 2010; 13)3);182-187.185.Table 1. Remission rates of 201 patients with dfferentDISCUSSIONbedridden levels (n, %)Degree of PersistentTreatment durationPathogenesis of constipation of posttraumatic bed-movement remission ≤1 week_ 1-2 weeks2 weeksridden patientsRareYes10 (43.48) 22 (73.33)70 (80.46)Of the 201 patients in our study, the number of maleNo13 (56.52) 8 (26.67)17 (19.54)patients was more than that of female patients and theSubtotal 23 (100.00 30 (100.00)87 (10.00)0mean age was less than 50 years, for trauma frequentlySlight6 (50.00) 7 (77.78)38 (95.00)happens to young aduts, which is significantly differ-Wo6(50.00) 2 (2.22)2 (5.00)ent from the demographic characteristics of populationSubtotal 12 (100.00) 9 (100.00) 40 (100.00)with chronic constipation. Besides, patients with a his-tory of constipation only accounted for 11.94%, andCMH test: mean value (one way dlinal-22.39, P0000.most of them developed constipation after confinementTable 2. Remission rates of 201 patients who reachedto bed. Mostafa12 has reported an incidence of consti-pation as high as 83% in 48 cases of critially ill pa-or failed to reach the treatment endpoint (n. %)Treatment Persistenttients with a normal diet, which also demonstrates thatendpoint remission≤1 week1-2 weeksconfinement to bed is an important factor for the devel-Reached Yes8(44.44) 19 (73.08) 108 (85.04)opment of constipation. Causes of confinement to bedNk10 (55.56) 7 (26.92)19 (14.96)after trauma in this study included lower extremity frac-Subtotal 18 (100.00) 26 (100.00) 127 (100.00)tures (51.74%), spinal cord fractures (27 .63%), pelvicfractures (6.47%) and so on. Other possible mecha-Failed8(47.06) 10 (76.92) 0 (0.00)nisms of constipation in such cases were listed as9 (52.94)3 (23.08)0 (0.00)follows: (1) inappropriate dietary habits, malabsorptionSubtotal 17 (100.00) 13 (100.00)resulting from blood loss and pain during posttraumaticCMH test: mean value (one way ordinal)=18.04, P-0.0000.period, or dehydrations caused by decreased fiber in-take and inadequate water intake; (2) psychologicalproblems or psychiatric disorders such as anxiety anddepression as a result of incapacitated self-care anddefecation in need of others' help especially; (3)changesof the living environment or being unaccustomed to def-ecating in bed in a lying position; (4) application of medications that may cause constipation; and (5) decreasedactivity12 due to absolute bedridden status. As a result01234567891011121314of trauma and surgery, 69.65% cases in the study wereFigure 1. Changes of defecation frequency after treatment withunable to move voluntarily and 30.35% could only movepolyethylene glycol 4000.slightly on the bed. In this study, 61.19% of the casestook drugs possibly causing constipation, such as pro-100%ton pump inhibitor (PPI). calcium channel blocker, anti-biotics, especially analgesics which can suppress bowel75movements and was significantly associated withconstipation.1350%25%Treatment of constipation of posttraumatic bedrid-den patientsThe treatment of constipation should aim at curing6 91011121314Daysthe priients' dietary struc-■No delecation■Bistoltypes1.2 Brsto trpes35 Bristol bpes6-7ture an中國煤化Iications shoud beFigure 2. Changes in the stool consistency after treatment withconsidTYHC N M H Gmptoms guided bythe principle that only drugs with minimum toxicity, sideeffects and drug dependence, such as leavening agents.186.Chinese Joumal of Traumatology 2010; 13/3):182-187and osmotic laxatives could be chosen. For patientstory of constipation and ability of slight movementin bed.with fecal impaction, symptoms should be first relievedby cleaning enema, or short-term administration of iriPatients with milder constipation showed a highertants before the aplication of leavening agents or 0S-remission rate. Remission rates for those with less thanmotic laxatives. For those with constipations causedthree times of defecation per week or stools of Bristolby long-term bedridden status, stimulants or lubricantstypes 1-2 before treatment were 74.86% and 72.92%could be used to relieve the short-term symptoms.respectively, which were significantly lower than the to-However, constipation may relapse due to persistenttal remission rate of this group (76.12%). The persistentexistence of inducing factors. Repeated use mayremission rate of patients with Bristol types 1-2 after theweaken the effectiveness of the above laxatives and2-week treatment was 81. 18%, lower than that of thoseresult in anorectal burning. The use of iritants maywith Bristol types 3-5 (92.86%). The persistent remis-cause abdominal cramp; a long-term use may lead tosion rate increased with the prolongation of treatment.melanosis colifs and cathartic colons and affect the ab-The remission rate was 85% for patients completing thesorption of fat soluble vitamins. In some severe cases,2-week treatment, while 78.95% for those reached thewater and electrolyte disorders may be arised, therebytreatmen endpoint, as polyethylene glycol 4000 is anaffecting the recovery of patients. Therefore, the first-osmotic laxative and needs a long-term administrationline treatments for constipation of bedridden patientsto keep the normal bowel movement. Patients withoutshould be osmotic and bulk forming laxatives, with theaccompanying symptoms had a higher remission rate.treatment goal set as one or two times of defecationPatients with a history of constipation and laxative medi-per day.3cation had a poorer remission rate. Patients who couldmove slighty in bed showed a remission rate as highPolyethylene glycol 4000 (Forlax), a long chainas 95% at the end of the second week, indicating thatpolymer with a high molecular weight, can conjugatean appropriate movement in bed should be advocated.with water molecule through hydrogen bond to increasethe water content and volume of stools, thereby, faciliAdverse drug reactions of polyethylene glycol 4000tate bowel movement and defecation.9 It is neitherinclude abdominal distension, abdominal pain, diarrheaabsorbed nor metabolized in the digestive tract, henceand nausea."7 During the treatment with polyethyleneit is highly safe and well tolerable. Thus, the long-termglycol 4000, 60 cases (29 85%) developed diarrhea as-medication is conducive to reconstruct the normal def-sociated with drug administration at different dosages.ecation pattern of patients, and has now been widelyThis indicates that it is necessary to adjust the dosageused for adult chronic functional constipation. 10.14 It haspromptly and individully accordingodiferentresponsesbeen reported to be more effective than lactulose15 andto drugs in order to ensure the overall efficacy of thesafer than Tegaserod1.drug. Only 2 patients complained of an abdominal pain,which was resolved spontaneously or after discontinu-Of the 201 patients treated with polyethylene glycolation of treatment. No allergic reaction was reported in4000, 194 (94.52%) showed remission of constipation,this trial, consistent with other studies7.18. 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