| Introduction:Nutritional support is an indispensable part of comprehensive treatments for critically ill patients. It is consensus that initiation of enteral nutrition should be started as early as possible in critical ill patients. However, gastric feeding may be unfavorable in critically ill patients because of regurgitation and aspiration. The post-pyloric route should be the routine way for critically ill patients with necessary instruments. However, percutaneous endoscopic jejunostomy, gastric surgery/jejunostomy, the intestinal fistula should not be the routine methods for critically ill patients requiring post-pyloric feeding. Although endoscopy or fluoroscopy-guided placement of nasojejunal tube are reliable, but they can not be the routine methods for their requirements of special instruments or equipments. The Flocare Bengmark naso-intestinal feeding tube is a self-propelled, spiral-ended nasojejunal feeding tube. It is special designed to facilitate transpyloric passage and migration into the jejunum by gastric and duodenal peristalsis. However, the gastric motilities are impaired in critically ill patients. In practice, prokinetic drugs are already used to facilitate gastric emptying in critically illness. We hypothesized that prokinetic agents can facilitate and accelerate the post-pyloric migration of the self-propelled feeding tube. This multicenter randomized controlled trial was implemented to determine whether metoclopramide or domperidone can improve the successful rate of post-pyloric placement of nasojejunal tube and to identify the potential factors facilitating post-pyloric placement of spiral nasojejunal tube in critically ill patientsMethods1. Study design and patientsWe performed a multicenter, prospective, randomized, controlled clinical trial, which was conducted in the ICUs of seven hospitals in China from Apr2,2012to Feb25,2014. In this study, stratified random sampling program was used. The block size was6. The method of randomization and block size were blinded until the data analysis was finished completely. Clinicians who enrolled the subjects were not involved in data collection. Eligible patients were randomly assigned in each hospital with two in each block assigned to the metoclopramide group and two assigned to the domperidone group and two assigned to the control group after telephone verification through a randomization center.2. The managements of the spiral nasojejunal tubes and the study drugsA self-propelled feeding tube (Flo-care Bengmark(?) CH10, Nutricia, the Netherlands) was used in the trial. All the intention to treat patients were nasally intubated with the nasojejunal tubes and gastric position of the tubes were checked by air insufflation. In the metoclopramide group, patients received metoclopramide before tube insertion. The dosages were10mg in patients with renal insufficiency. In the domperidone group, patients received nasogastric feeding of80mg domperidone after the tube was inserted. In the control group the patients received no prokinetic agents.3. Confirmation the position of the tube24hours after initial placement, feeding tube placement was confirmed by abdominal X-ray in each patients with the help of the meglumine diatrizoate. The position of the tube was adjudicated by an independent panel of radiological and ICU experts blinded to the treatment assignments.4. Outcomes and data collectionThe primary end point of this study was the success rate of post-pyloric migration of the tubes. Secondary outcomes included the proportion of migration of the tubes into the second portion, third portion, forth portion of the duodenum and the jejunum and the migration distances of the nasojejunal tubes. Once the position of the tubes were confirmed, patients’data including demographic characteristic, primary diagnose, APACHE II scores, SOFA scores, initial scale of the placement, assigned group, sedative drug, vasoactive drug delivered over24h after tube insertion, the position of tube’ tip were recorded. Adverse events were recorded as drug-related adverse events and tube-related adverse events. All the data was recorded in the case report form.5. Statistical analysis and sample sizeBased on a previous study, a sample size of279patients was required with a two-sided test (a error=5%; power=80%). Considering a possible drop-out rate of10%, the trial wound need to enroll307patients in total. Demographic data, outcome data were summarized by frequency for categorical variables and mean±standard deviation (SD) or median with interquartile range (IQR) for continuous variables. Proportions were compared with chi-square test. Continuous variable were tested by means of t test with normal distribution or Kruskal-Wallis H test with non-normal distribution. The patients were stratified on a number of baseline covariates such as mechanical ventilation, sedative, analgesic agent and so on. We compared the primary outcome among each group in different prespecified subgroups. Application of Logistic multivariate stepwise regression (forward) into the factors determining the final model. Consistent with the intention-to-treat principle, all analyses were based on all available population, neither making any assumption nor imputing the missing data. Statistical analysis was carried out using SPSS v13.0for windows (SPSS Inc, Chicago, IL). Two sided P values were reported and a P value less than0.05was considered as statistically significant. In pairwise comparisons between the three groups, a P value less than0.016was considered as statistically significant.Result1. Study profileBetween Apr2,2012and Feb25,2014,307eligible patients were randomized. Before intubation of the nasojejunal tube9patients were excluded from the trial. In the metoclopramide group, three patients were excluded. In the domperidone group, one patients were excluded. In the control group, five patients were excluded. A total of298patients were intubated the nasojejunal tube. In the metoclopramide group,95patients completed the trial according the protocol regarding the use of20mg metoclopramide, while5received10mg metoclopramide because of renal insufficient. In the domperidone group,93patients completed the trial with the protocol regarding the use of80mg domperidone, while6received40mg because they were transferred out of ICU within24hours after initial placement of the tubes. All the patients were followed up for entire24-hour study period without drop-out.2. Baseline dataAll the groups had similar characteristics in most demographic and baseline variables. Baseline characteristic data, such as sedative, vasoactive drugs, mechanical ventilation, APACHE Ⅱ score, SOFA score were comparable among the groups. 3. Study outcomesPrimary outcomeThe success rate of post-pyloric placement was55.0%in the metoclopramide group,51.5%in the domperidone group,27.3%in the control group. There was significant difference in the success rate of post-pyloric placement among the three groups (χ2=18.320,p=0.0001). The success rate of post-pyloric placement was higher in the metoclopramide group than in the control group (OR,3.3;95%CI1.8-5.9; P=0.0001). The success rate of post-pyloric placement was higher in the domperidone group than in the control group (OR,2.8;95%CI1.6-5.1; P=0.0005). There was no significant difference in the success rate of post-pyloric placement between the metoclopramide group and the domperidone group. Secondary outcomesFor all patients in the metoclopramide group with successful placements of the tubes, migration into the first portion of the duodenum was found in8patients, the second portion in13patients, the third portion in7patients, the forth portion in8patients, the jejunum in19patients. The successful rate of spontaneous migration beyond the second portion of duodenum, beyond the third portion of duodenum, beyond the forth portion of duodenum was higher in the metoclopramide group than in the control group with significant difference. The successful rate of spontaneous migration into jejunum was higher in the metoclopramide group than in the control group with no significant difference (OR,2.1;95%CI0.9-4.8;P=0.0752). For all patients in the domperidone group with successful placement of the tube, migration into the first portion of the duodenum was found in7patients, the second portion in4patients, the third portion in14patients, the forth portion in10patients, the jejunum in16patients. The successful rate of spontaneous migration beyond the second portion of duodenum, beyond the third portion of duodenum, beyond the forth portion of duodenum was higher in the domperidone group than in the control group with significant difference. The successful rate of spontaneous migration into jejunum was higher in the domperidone group than in the control group with on significant difference (OR,1.7;95%CI0.7-4.0; P=0.2068).There was no significant difference in the initial scale of the nasojejunal tube among the three groups.24hours after initial placement, all the tubes in three groups had migrated. There was significant difference in the migration distance among the three groups. The migration distance was significant longer in the metoclopramide group than in the control group, the mean difference was5.3cm (95%CI1.9-8.7, p<0.01). the migration distance was significant longer in the domperidone group than in the control group, the mean difference was4.3cm (95%CI0.9-7.7, P<0.01). There was no significant difference in the migration distance between the metoclopramide group and the domperidone group.Subgroup analysisPrespecified analyses of the primary end point, where patients were stratified according to APACHE Ⅱ score, SOFA score, mechanical ventilation, neurological diseases, sepsis, sedative drug, vasoactive drug, age and sex, showed that the successful rate was higher in the metoclopramide group and in the domperidone group than in the control group. In a subgroup analysis of patients with APACHE Ⅱ<20,SOFA≥12, non-neurological diseases, non-sepsis or sepsis, without sedative, without vasoactive drug, without mechanical ventilation, age≥60or age<20, male patients the successful rate was significant higher in the metoclopramide group and in the domperidone group than in the control group. In a subgroup analysis of patients with neurological diseases, SOFA<12, the successful rate was higher in the metoclopramide group than in the control group. In patients with APACHE Ⅱ≥20, sedative, vasoactive drug and female patients, there was no significant difference in the successful rate of post-pyloric placement among metoclopramide group and domperidone group and control group.5. Risk factors for the successful rate of post-pyloric placementMultivariate logistic regression identified that APACHEⅡ<20, SOFA<12， use of prokinetic agents, without vasoactive drug were independent factors facilitating the post-pyloric placement of nasojejunal tubes.6. Adverse eventsAll298patients in the intention-to-treat population were included in the safety evaluation. Safety assessment of drugs and spiral nasojejunal tube were based on the comparison of all adverse events recorded from the three groups The incidence of drug-related and intubation-related adverse events was similar among each groupConclusions1. use of metoclopramide or domperidone can improve the successful rate of post-pyloric placement of spiral nasojejunal tubes.2. The successful rate of spontaneous migration beyond the second portion of duodenum, beyond the third portion of duodenum, beyond the forth portion of duodenum can be improved by metoclopramide or domperidone.3. The migration distance can be significantly improved by metoclopramide or domperidone4. There was not any serious drug related adverse event.5. APACHE II<20, SOFA<12, use of prokinetic agents, without vasoactive drug were independent factors facilitating post-pyloric placement of nasojejunal tubes. |
PDF Full Text Request