Comparison of cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition in critically III, mechanically ventilated adults.

BACKGROUND: Placebo-controlled studies have indicated that both cisapride and metoclopramide promote gastric motility in critically ill patients. Objective: This study was conducted to compare cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition (EN) and to evaluate the relationship between aspirated gastric residual volume and gastric emptying function in this patient population. METHODS: In this double-blind study, critically ill, mechanically ventilated patients with an aspirated gastric residual volume > or = 150 mL while receiving intragastric EN were randomized to receive enteral cisapride 10 mg or metoclopramide 10 mg every 6 hours for a total of 7 doses. The acetaminophen-absorption method was used to assess gastric emptying at baseline and 30 minutes after the seventh dose by determining the area under the plasma concentration-time curve at 240 minutes (AUC240), maximum concentration (Cmax), and time to Cmax (Tmax). Gastric residual volume was measured every 6 hours before dosing. RESULTS: Fourteen patients were included in the study, 7 in each group. Patient characteristics were similar in the 2 groups. Compared with baseline, metoclopramide significantly accelerated Tmax (39.00 +/- 15.56 min with metoclopramide vs 103.71 +/- 47.35 min at baseline; P = 0.018) and increased Cmax (12.94 +/- 6.68 mg/L vs 6.97 +/- 4.78 mg/L; P = 0.018) and AUC240 (1,421.43 +/- 780.31 mg/L x min vs 839.00 +/- 545.58 mg/L x min; P = 0.043). Cisapride increased Cmax from baseline (12.27 +/- 8.95 mg/L vs 4.53 +/- 2.37 mg/L, respectively), but the difference was not statistically significant. Gastric residual volume was significantly reduced from baseline after 3 doses of metoclopramide (from 268.7 +/- 112.3 mL to 57.0 +/- 23.1 mL; P < 0.05) and was significantly lower after the seventh dose of metoclopramide than after the seventh dose of cisapride (5.3 +/- 8.2 mL vs 41.4 +/- 39.7 mL, respectively; P = 0.05). Cmax at baseline and residual volume at study entry were inversely correlated (r = -0.50; P = 0.049). Conclusions: Both cisapride and metoclopramide enhanced gastric motility and improved tolerance to intragastric EN. Metoclopramide reduced gastric residual volume to a significantly greater extent than did cisapride. Only Cmax at baseline was inversely associated with residual volume.     

Erythromycin improves gastric emptying in critically ill patients intolerant of nasogastric feeding

OBJECTIVE: To evaluate the effect of intravenous erythromycin on gastric emptying and the success of enteral feeding in mechanically ventilated, critically ill patients with large volume gastric aspirates. DESIGN: Prospective, double-blind, randomized, and placebo-controlled trial. SETTING: General intensive care unit in a university hospital. PATIENTS: Twenty critically ill, mechanically ventilated patients intolerant of nasogastric feeding (indicated by a residual gastric volume of > or =250 mL during feed administration at > or =40 mL/hr). INTERVENTIONS: After a gastric aspirate of > or =250 mL, which was discarded, the enteral feeding was continued at the previous rate for 3 hrs. Intravenous erythromycin (200 mg) or placebo was then administered over 20 mins. The residual gastric contents were again aspirated and the volume was recorded 1 hr after the infusion began. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was calculated as volume of feed infused into the stomach over 4 hrs minus the residual volume aspirated. Mean gastric emptying was 139+/-37 (+/-SEM) mL after erythromycin and -2+/-46 mL after placebo (p = .027). Nasogastric feeding was successful in nine of ten patients treated with erythromycin and five of ten who received placebo 1 hr after infusion (chi-square p = .05). CONCLUSION: In critically ill patients who have large volumes of gastric aspirates indicating a failure to tolerate nasogastric feeding, a single small dose of intravenous erythromycin allows continuation of feed in the short term.     

Erythromycin and early enteral nutrition in mechanically ventilated patients

OBJECTIVE: To determine whether erythromycin facilitates early enteral nutrition in mechanically ventilated, critically ill patients. DESIGN: Prospective, randomized, placebo-controlled, single-blind trial. SETTING: General intensive care unit in a university-affiliated general hospital. PATIENTS: Forty consecutive critically ill patients receiving invasive mechanical ventilation and early nasogastric feeding. INTERVENTIONS: Patients were assigned randomly to intravenous erythromycin (250 mg/6 hrs; n = 20) or a placebo (intravenous 5% dextrose, 50 mL/6 hrs; n = 20) for 5 days. The first erythromycin or 5% dextrose injection was given at 8 am on the day after intubation. One hour later, a daily 18-hr enteral nutrition regimen via a 14-Fr gastric tube was started. Residual gastric volume was aspirated and measured every day at 9 am, 3 pm, 9 pm, and 3 am. Enteral nutrition was discontinued if residual gastric volume exceeded 250 mL or the patient vomited. MEASUREMENTS AND MAIN RESULTS: On the first day, residual gastric volume was smaller in the erythromycin than in the placebo group (3 pm, 15 +/- 7 mL vs. 52 +/- 14 mL, p <.05; 9 pm, 29 +/- 15 mL vs. 100 +/- 20 mL, p <.001; 3 am, 11 +/- 4 mL vs. 54 +/- 13 mL, p <.05). With erythromycin, residual gastric volume at 9 pm was smaller on the second day (33 +/- 11 mL vs. 83 +/- 19 mL, p <.01) and residual gastric volume at 3 pm was smaller on the third day (39 +/- 15 mL vs. 88 +/- 19 mL, p <.05) than with placebo. On the fourth and fifth days, the differences in residual gastric volume were not significant. Enteral nutrition was discontinued before the end of the 5-day period in seven of the 20 erythromycin patients and 14 of the 20 placebo patients (p <.001). CONCLUSION: In critically ill patients receiving invasive mechanical ventilation, erythromycin promotes gastric emptying and improves the chances of successful early enteral nutrition.     

Metoclopramide for preventing pneumonia in critically ill patients receiving enteral tube feeding: a randomized controlled trial

OBJECTIVE: To determine whether metoclopramide prevents nosocomial pneumonia in intensive care unit (ICU) patients receiving enteral feeding by a nasogastric tube. DESIGN: Prospective, randomized, controlled trial. SETTING: ICU of a university hospital. PATIENTS: A total of 305 consecutive patients requiring placement of a nasogastric tube for >24 hrs. INTERVENTIONS: Patients were randomized to receive either 10 mg of metoclopramide or placebo at 8-hr intervals through the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: A total of 174 patients received placebo and 131 received metoclopramide. Baseline characteristics in the two treatment groups were comparable. Of the 305 patients, 46 developed nosocomial pneumonia, which was 24 patients (13.7%) in the placebo group and 22 (16.8%) in the metoclopramide group (p > .05). Patients in the placebo group developed pneumonia earlier than patients receiving metoclopramide (4.46+/-1.72 days [mean +/- SD[rsqb] after ICU admission compared with 5.95+/-1.78 days; p = .006). Subgroup analysis showed that metoclopramide did not reduce the frequency rate of pneumonia in patients with tracheal intubation (19 [25.3%] of 75 patients receiving metoclopramide vs. 21 [21.2%] of 99 patients receiving placebo) or those receiving mechanical ventilation (17 [25.6%] of 58 patients receiving metoclopramide vs. 20 [29.3%] of 78 patients receiving placebo). The mortality rate also did not differ in the two treatments groups (56% in the metoclopramide group vs. 53% in the placebo group; p > .05). CONCLUSIONS: Although metoclopramide delayed the development of nosocomial pneumonia, it did not decrease its frequency rate and had no effect on the mortality rate in critically ill patients receiving nasogastric enteral feeding.     

Prokinetic therapy for feed intolerance in critical illness: one drug or two?

OBJECTIVE: To compare the efficacy of combination therapy, with erythromycin and metoclopramide, to erythromycin alone in the treatment of feed intolerance in critically ill patients. DESIGN: Randomized, controlled, double-blind trial. SETTING: Mixed medical and surgical intensive care unit. PATIENTS: Seventy-five mechanically ventilated, medical patients with feed intolerance (gastric residual volume > or =250 mL). INTERVENTIONS: Patients received either combination therapy (n = 37; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily) or erythromycin alone (n = 38; 200 mg of intravenous erythromycin twice daily) in a prospective, randomized fashion. Gastric feeding was re-commenced and 6-hourly gastric aspirates performed. Patients were studied for 7 days. Successful feeding was defined as a gastric residual volume <250 mL with the feeding rate > or =40 mL/hr, over 7 days. Secondary outcomes included daily caloric intake, vomiting, postpyloric feeding, length of stay, and mortality. MEASUREMENTS AND MAIN RESULTS: Demographic data; use of inotropes, opioids, or benzodiazepines; and pretreatment gastric residual volume were similar between the two groups. The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy, compared with erythromycin alone (136 +/- 23 mL vs. 293 +/- 45 mL, p = .04). Over the 7 days, patients treated with combination therapy had greater feeding success, received more daily calories, and had a lower requirement for postpyloric feeding, compared with erythromycin alone. Tachyphylaxis occurred in both groups but was less with combination therapy. Sedation, higher pretreatment gastric residual volume, and hypoalbuminemia were significantly associated with a poor response. There was no difference in the length of hospital stay or mortality rate between the groups. Watery diarrhea was more common with combination therapy (20 of 37 vs. 10 of 38, p = .01) but was not associated with enteric infections, including Clostridium difficile. CONCLUSIONS: In critically ill patients with feed intolerance, combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment.     

Early enteral nutrition in mechanically ventilated patients in the prone position

OBJECTIVE: To assess the tolerance of early enteral nutrition in critically ill patients receiving invasive mechanical ventilation in the prone position. DESIGN: Prospective, comparative study. SETTING: General intensive care unit in a university-affiliated hospital. PATIENTS: A total of 71 consecutive patients receiving invasive mechanical ventilation with early nasogastric enteral nutrition were studied for 5 days while being treated continuously in the supine position (supine position group, n = 37) or with intermittent prone positioning for severe hypoxemia (prone position group, n = 34). INTERVENTIONS: Inclusion occurred within 24 hrs of mechanical ventilation initiation. Daily 18-hr enteral nutrition via a 14F gastric tube was initiated. Prone position patients were turned every 6 hrs as long as PaO2/FiO2 remained at <150, with a FiO2 of 0.6 and positive end-expiratory pressure of 10; the head was slightly elevated. When supine, patients in both groups were semirecumbent. Residual gastric volume was measured every 6 hrs, and enteral nutrition was discontinued if it exceeded 250 mL or vomiting occurred. MEASUREMENTS AND MAIN RESULTS: The groups were similar for age, sex, Simplified Acute Physiology Score II, mortality, and risk factors for enteral nutrition intolerance. At baseline, PaO2/FiO2 was lower in prone position patients than in supine position patients (127 +/- 55 vs. 228 +/- 102; p <.001). As compared with supine position patients, prone position patients had significantly greater residual gastric volumes on days 1, 2, and 4 and experienced more vomiting episodes (median, 1 [interquartile range, 0-2] vs. 0 [interquartile range, 0-1]; p <.05). Enteral nutrition was stopped in 82% of prone position patients and 49% of supine position patients (p <.01) so that daily enteral nutrition volumes were lower with prone position patients. In the prone position group, vomiting occurred more frequently in the prone than in the supine position (relative risk, 2.5; 95% confidence interval, 1.5-4.0; p <.001). CONCLUSION: In critically ill patients receiving invasive mechanical ventilation in the prone position, early enteral nutrition is poorly tolerated. Prokinetic agents or transpyloric feeding and semirecumbency should be considered to enhance gastric emptying and to prevent vomiting in patients receiving mechanical ventilation in the prone position.     

红霉素和甲氧氯普胺治疗重症监护病房患者胃排空障碍的研究

目的 观察红霉紊、甲氧氯普胺单用或联用治疗重症监护病房(ICU)患者胃排空障碍的作用.方法 收集2007年1月至2009年1月在ICU需要早期肠内营养支持＞7 d的患者152例,并按随机数字表法分为红霉素组(200 mg静脉滴注,12 h 1次)、甲氧氯普胺组(10 mg静脉注射,8 h 1次)及红霉素和甲氧氯普胺联用组,共给药7 d.记录基本情况以及每日03:00、09:00、15:00和21:00患者的胃液潴留量;比较各组每日胃液潴留量及肠内营养喂养成功率的变化;并筛选影响红霉素和甲氧氯普胺起作用的独立相关因素.结果 联合治疗组每日胃液潴留量最少(最高达(40±8)ml],红霉素组次之[最高达(42±7)ml],甲氧氯普胺组最多[最高达(59±8)ml,P＜0.05或P＜0.01).联合治疗组的喂养成功率最高(最高达97.4%),其次为红霉素组(最高达90.0%),甲氧氯普胺组最低(最高达89.5%,P＜0.05或P＜0.01).肠内营养前24 h的胃液潴留量(r=-0.584,P=0.000)、高血糖水平(r=-0.345,P=0.029)、高急性生理学与慢性健康状况评分系统Ⅰ(APACHE Ⅱ)评分(r=-0.437,P=0.005)、血管收缩药物使用(r=-0.389,P=0.041)为影响肠道动力药物起作用的独立相关因素.结论 小剂量红霉素能提高ICU患者肠内营养喂养成功率;而且红霉素加甲氧氯普胺联合治疗胃排空障碍效果最佳,且不良反应小.     

Metoclopramide improves gastric motility in critically ill patients

Objective: To assess the effect of metoclopramide on gastric motility in critically ill patients. Design: Prospective, controlled, single-blind cross-over trial. Setting: A 10-bed general intensive care unit. Patients: Ten critically ill, enterally fed adult patients without renal failure. Interventions: Each patient received enteral feeding with Enrich via a nasogastric tube at 50 ml/h throughout the 5-h study period on two consecutive days. Either normal saline (control) or 10 mg of metoclopramide (treatment) was administered intravenously at the start of the study period in random order with cross-over design. Measurements and results: Gastric motility was measured indirectly by analysis of the absorption over time of 1.5 g of paracetamol administered into the stomach at the start of the study period together with a 100 ml bolus of Enrich feed. The rate of gastric emptying is proportional to the area under the line plot of serum paracetamol concentration against time over 120 min (AUC120). Eight of the ten patients studied showed an increased AUC120 with metoclopramide compared to that with saline. Statistical analysis with the Wilcoxon signed rank test gave a p value of 0.04, indicating a significant increase in gastric emptying following administration of metoclopramide. Conclusions: The administration of intravenous metoclopramide improved gastric emptying in a heterogeneous group of critically ill patients. Metoclopramide is a useful prokinetic drug in this patient population. Final revision received: 18 January 1999 Accepted: 2 March 1999     

Erythromycin dose of 70 mg accelerates gastric emptying as effectively as 200 mg in the critically ill

Objective To compare the effectiveness of 70-mg and 200-mg doses of intravenous erythromycin in improving gastric emptying in critically ill patients.Design Gastric emptying was measured on consecutive days; day 1 (pre-treatment), day 2 (post-treatment) after an intravenous infusion of either 70 or 200 mg erythromycin or saline placebo (0.9%), in a randomized double-blind fashion.Setting Mixed medical/surgical intensive care unit, tertiary referral.Patients and participants Thirty-five randomly selected, mechanically ventilated, enterally fed critically ill patients (median APACHE II score 19 on admission).Interventions On day 2 either 70 or 200 mg erythromycin or saline was administered intravenously over 20 min.Measurements and results Gastric emptying was measured using the [¹³C]octanoic acid breath test. The gastric emptying coefficient (GEC) and half-emptying time (t_1/2) were calculated from the area under the ¹³CO₂-recovery curve. Pre-treatment gastric emptying measurements were similar in all three patient groups. Treatment with both doses of erythromycin significantly reduced the gastric t_1/2: 70 mg, 98 min (IQR 88–112); 200 mg, 86 min (75–104); vs. placebo, 122 min (102–190) (p<0.05). The GEC was higher with both doses of erythromycin: 70 mg, 3.8 (3.3–4.0); 200 mg, 4.0 (3.6–4.2); vs. placebo, 2.9 (2.5–3.7) (p<0.05). There was no difference in gastric emptying post-treatment between the two doses of erythromycin. The effect of erythromycin was greatest in patients with delayed gastric emptying.Conclusions Treatment with 70 and 200 mg intravenous erythromycin are equally effective in accelerating gastric emptying in the critically ill     

The use of tegaserod in critically ill patients with impaired gastric motility

Studies have shown that early enteral nutrition in critically ill patients reduces the incidence of morbidity and death. Nonetheless, intolerance to gastric enteral nutrition is common in these patients as a result of gastroparesis. The use of prokinetic agents such as metoclopramide, domperidone, cisapride, and erythromycin can improve gastric emptying, but these agents are not without deleterious adverse effects. Tegaserod, a selective serotonin type 4 receptor partial agonist, was recently approved for treatment of women with irritable bowel syndrome. On the basis of tegaserod's mechanism of action, it was hypothesized that tegaserod may accelerate the return of gastric function in intensive care unit patients with gastroparesis. It would thus provide an additional agent for the management of gastroparesis with a more favorable safety profile. We present 3 case reports of the successful use of tegaserod in intensive care unit patients with impaired gastric motility. To our knowledge, the use of tegaserod in this setting has not been reported or studied previously.     

Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects

BACKGROUND: Acute hyperglycemia has been associated with delayed gastric emptying of solid foods in healthy control subjects. Erythromycin has been found to be a gastrointestinal prokinetic agent in humans. We examined whether acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of a solid meal after a fasted state in healthy subjects. METHODS: Twelve healthy subjects ate standard solid meals that had been radiolabeled. Gastric emptying was measured by scintigraphy during normoglycemia (5-8.9 mmol/L glucose) and hyperglycemia induced by intravenous glucose (16-19 mmol/L glucose) after administration of placebo or 200 mg of erythromycin intravenously. Emptying was measured randomly on 4 different days. RESULTS: Administration of erythromycin during normoglycemia or induced hyperglycemia compared with placebo accelerated the gastric emptying of the solid meal but did not completely normalize the delay caused by hyperglycemia versus normoglycemia (p < 0.001). In both conditions, erythromycin versus placebo significantly reduced the lag-phase duration (9.7 +/- 2.3 min and 22.0 +/- 3.9 min vs. 38.3 +/- 5.7 min and 49.5 +/- 6.0 min, respectively; p < 0.001), gastric emptying of the half meal (39.2 +/- 4.0 min and 52.0 +/- 7.1 min vs. 75.7 +/- 11.8 min and 94.0 +/- 13.4 min, respectively; p < 0.001), and the percentage of meal retained in the stomach 120 min postprandially (p < 0.001). CONCLUSION: The erythromycin-induced acceleration effect on gastric emptying was related to the plasma glucose level. Hyperglycemia might have chosen a cholinergic antagonist pathway that delayed gastric emptying of solids. Even though induced hyperglycemia inhibited gastric emptying, erythromycin accelerated the gastric emptying rate through two distinct pathways: cholinergic and noncholinergic.     

Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test

OBJECTIVE: To measure gastric emptying in ventilated critically ill patients with a new noninvasive breath test. DESIGN: Single-center, open study. SETTING: Combined medical and surgical intensive care unit of a university hospital. SUBJECTS: Thirty unselected mechanically ventilated critically ill patients receiving gastric feeding and 22 healthy volunteers. INTERVENTIONS: None. PATIENTS: After 4 hrs without feeding, intragastric infusion of 100 mL of a liquid meal (Ensure) labeled with 100 microL 13C-octanoic acid. End-expiratory breath samples were collected into evacuated tubes from the respirator circuit every 5 mins for the first hour, then every 15 mins for 3 hrs. End-expiratory breath samples were also collected from volunteers studied supine after an overnight fast following an identical infusion via a nasogastric tube. Breath 13CO2 was measured with an isotope ratio mass spectrometer. MEASUREMENTS AND MAIN RESULTS: Performance of the breath test posed no difficulty or interference with patient care. The CO2 level was >1% in 1297/1300 breath samples, indicating satisfactory end-expiratory timing. Data are median and interquartile range. Gastric emptying was slower in patients compared with volunteers: gastric emptying coefficient 2.93 (2.17-3.39) vs. 3.58 (3.18-3.79), p <.001 and gastric half emptying time, derived from the area under the 13CO2 curve, 155 min (130-220) vs. 133 min (120-145), p <.008. Fourteen of the 30 patients had a gastric emptying coefficient <95% of all volunteers and 11 had a gastric half emptying time longer than 95% of all volunteers. The Acute Physiology and Chronic Health Evaluation (APACHE II) score (median 22, range 13-43) either at admission or on the day of the study did not correlate with gastric emptying coefficient. CONCLUSION: Gastric emptying of a calorie-dense liquid meal is slow in 40% to 45% of unselected mechanically ventilated patients in a combined medical and surgical intensive care unit. The 13C-octanoic acid breath test is a novel and useful bedside technique to measure gastric emptying in these patients.     

Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness

OBJECTIVE: This study aimed to a) compare the efficacy of metoclopramide and erythromycin in the treatment of feed intolerance in critical illness; and b) determine the effectiveness of "rescue" combination therapy in patients who fail monotherapy. DESIGN: Randomized controlled trial. SETTING: Level III mixed medical and surgical intensive care unit. PATIENTS: Ninety mechanically ventilated, medical patients with feed-intolerance (gastric residual volume>or=250 mL). INTERVENTIONS: Patients received either metoclopramide 10 mg intravenously four times daily (n=45) or erythromycin 200 mg intravenously twice a day (n=45) in a double-blind, randomized fashion. After the first dose, nasogastric feeding was commenced and 6-hourly nasogastric aspirates were performed. If a gastric residual volume>or=250 mL recurred on treatment, open-label, combination therapy was given. Patients were studied for 7 days. Successful feeding was defined as 6-hourly gastric residual volume<250 mL with a feeding rate>or=40 mL/hr. MEASUREMENTS AND MAIN RESULTS: Demographic data, blood glucose levels, and use of inotropes, opioids, and benzodiazepines were similar between the two groups. After 24 hrs of treatment, both monotherapies reduced the mean gastric residual volume (metoclopramide, 830+/-32 mL to 435+/-30 mL, p<.0001; erythromycin, 798+/-33 mL to 201+/-19 mL, p<.0001) and improved the proportion of patients with successful feeding (metoclopramide=62% and erythromycin=87%). Treatment with erythromycin was more effective than metoclopramide, but the effectiveness of both treatments declined rapidly over time. In patients who failed monotherapy, rescue combination therapy was highly effective (day 1=92%) and maintained its effectiveness for the study duration (day 6=67%). High pretreatment gastric residual volume was associated with poor response to prokinetic therapy. CONCLUSIONS: In critical illness, erythromycin is more effective than metoclopramide in treating feed intolerance, but the rapid decline in effectiveness renders both treatments suboptimal. Rescue combination therapy is highly effective, and further study is required to examine its role as the first-line therapy.     

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations

OBJECTIVE: Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients. DESIGN: Randomized, controlled trial. SETTING: Level 3, mixed medical and surgical intensive care unit. SUBJECTS: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). INTERVENTIONS: Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion. MEASUREMENTS AND MAIN RESULTS: Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients. CONCLUSIONS: Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.     

Gastric residual volumes in critically ill paediatric patients: a comparison of feeding regimens.

This study examined the effect of gastric feeding regimens, either continuous or intermittent, on fourth hourly gastric residual volumes (GRV) in a group of critically ill paediatric patients where delayed gastric emptying is defined as a GRV greater than 5ml/kg. A randomised controlled trial was conducted in a tertiary paediatric intensive care unit (PICU), with 45 participants being randomly assigned to either the continuous (n=22) or intermittent (n=23) gastric feeding groups. Participants remained in the assigned group for the duration of the study and, fourth hourly, GRV were assessed to monitor the incidence of delayed gastric emptying. Both groups were similar in age, weight, gender, diagnosis, paediatric index mortality (PIM) score, and usage of pharmacological agents known to affect the gastrointestinal tract. No differences emerged in study duration or the volume of administered enteral formula (ml/kg/day). The intermittent feeding group commenced enteral feeding earlier in the PICU admission (13.0 hours versus 18.5 hrs, p=0.05). Repeated measures analysis revealed no overall difference in median GRV/kg values between treatment groups over the 72 hour study period. Additionally, the incidence of fourth hourly GRV, greater than 5ml/kg, was not different between the continuous and intermittent feeding groups. The provision of enteral nutrition via the gastric route is a common treatment in the PICU, and GRV are frequently used as a measure of gastric tolerance. The result of this analysis provides some support for the theoretical definition of delayed gastric emptying being >5ml/kg. However, further work is required to confirm this finding and to determine its relevance when providing enteral nutrition to the critically ill paediatric patient.     

Establishment of enteral nutrition: prokinetic agents and small bowel feeding tubes

PURPOSE OF REVIEW: Nutritional support is vital to improving the clinical outcomes in patients in the intensive care unit. Enteral nutrition should be administered early and aggressively, thereby reducing the need for parenteral nutrition. Because nasogastric feeding is often associated with gastrointestinal intolerance, recent research has focused on the use of prokinetic agents or small bowel feeding tubes to enhance the successful establishment and maintenance of enteral nutrition. RECENT FINDINGS: Prokinetic agents (such as metoclopramide and erythromycin) improve markers of gastric emptying and appear to improve tolerance of enteral nutrition, although their effects on clinical outcomes are not as well established. In comparison with nasogastric feeding, small bowel feeding allows the dysfunctional stomach of the critically ill to be bypassed, thereby reducing the rate of gastrointestinal complications and probably the risk of pneumonia. Small bowel tubes are more difficult to place than nasogastric tubes, although the new Tiger tube appears very promising. SUMMARY: Nasogastric feeding is preferred for almost all patients in the intensive care unit. Metoclopramide is the preferred prokinetic agent, although whether it or erythromycin should be administered to all patients in the intensive care unit or only those with gastrointestinal intolerance remains unknown. Small bowel feeding is not currently recommended for all patients in the intensive care unit because the benefits do not appear to outweigh the logistic and cost considerations. Nevertheless, when gastrointestinal intolerance develops in a nasogastrically fed patient, a small bowel feeding tube should be inserted at the earliest opportunity.     

Intravenous erythromycin facilitates bedside placement of postpyloric feeding tubes in critically ill adults: a double-blind,randomized, placebo-controlled study

OBJECTIVE To evaluate the efficacy of intravenous erythromycin as a method to facilitate feeding tube placement into the small intestine in critically ill patients.DESIGN Double blind, randomized, controlled trial.SETTING Medical and surgical intensive care units in an academic medical center.PATIENTS Prospective cohort of 36 consecutive adults requiring intensive care unit care and enteral tube feeding for nutritional support.INTERVENTION Infusion of a single dose of intravenous erythromycin (500 mg) or saline before placement of 10-Fr feeding tubes using a standardized active bedside protocol.MEASUREMENTS AND MAIN RESULTS We determined the success rate of feeding tube placement into or beyond the second portion of the duodenum and the time required for this procedure by experienced nurses. The feeding tube was considered to be postpyloric when the tip was in the second portion of the duodenum or beyond. The predictive value of a serial step-up in gastrointestinal aspirate pH from < or = 5.0 to > or = 6.0 was also determined. Use of intravenous erythromycin significantly improved the rate of feeding tube placement into the duodenum or jejunum (erythromycin group, 13 of 14 patients or 93% vs. the control group, 12 of 22 patients or 55%; p < .03). Erythromycin administration also significantly decreased the procedure time from 25 +/- 3 to 15 +/- 2 mins (p < .04). Feeding tube placement into either duodenum or jejunum was confirmed in all 18 patients with a pH step-up from < or = 5.0 to > or = 6.0. CONCLUSION: A single bolus dose of intravenous erythromycin facilitates active bedside placement of postpyloric feeding tubes in critically ill adult patients.     

Relationship of serotonin-3 receptor antagonist activity to gastric emptying and motor-stimulating actions of prokinetic drugs in dogs

Drugs that enhance gastrointestinal motility include the benzamide drugs metoclopramide, cisapride and renzapride (BRL-24924). Because these agents also are serotonin-3 (5-HT3) receptor antagonists, which can promote gastric emptying in some species, the motor-stimulating properties of benzamide agents may be due to this mechanism. Metoclopramide (0.3-3.0 mg/kg i.v.), cisapride (0.03-1.0 mg/kg i.v.) and BRL-24924 (0.01-0.1 mg/kg i.v.) were evaluated for their relative motility-stimulating and 5-HT3 receptor antagonist activities in conscious dogs and were compared with selective 5-HT3 antagonist antiemetic compounds ICS-205-930, (3 alpha-tropanyl)1-H-indole-3-carboxylic acid ester and granisetron (BRL-43694). Gastric antral contractions and intestinal myoelectric motility were determined in response to drugs, as were their effects on solid and liquid emptying in a gamma scintigraphic model of gastroparesis. 5-HT3 receptor antagonist potency was examined by deriving ED50 values for inhibition of cisplatin emesis. All drugs were 5-HT3 antagonists as they blocked cisplatin emesis with relative potencies of BRL-43694 = ICS-205-930 greater than BRL-24924 greater than cisapride = metoclopramide. The order of potency for stimulating fasted dog antral contractile activity, however, was BRL-24924 = cisapride greater than metoclopramide greater than ICS-205-930 = BRL-43694. Maximally effective doses of BRL-24924 (0.1 mg/kg i.v.) and cisapride (0.67 mg/kg i.v.) in the antrum also stimulated intestinal myoelectrical activity, whereas ICS-205-930 (0.5 and 2.0 mg/kg i.v.) was not active.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amylin is associated with delayed gastric emptying in critically ill children

OBJECTIVES: Amylin is a novel 37 amino acid that is secreted together with insulin from the pancreas in response to enteral nutrient intake. As a potent inhibitor of gastric motility it plays an important role in the control of carbohydrate absorption. In this study we aimed to determine the relationship between amylin levels and gastric emptying in critically ill children. DESIGN: Prospective interventional study. SETTING: Tertiary paediatric intensive care unit. PATIENTS: Twenty-three patients were studied following admission to a paediatric intensive care unit. The median age (25th-75th centiles) was 5.8 years (1.5-11.6) and weight 20 kg (12.8-47.5). INTERVENTIONS: Patients were defined as feed-intolerant on the basis of gastric residual volume greater than 125% 4 h after a feed challenge. Three objective measures of gastric emptying were then calculated from a 6 h paracetamol absorption test. Blood glucose, serum insulin and amylin levels were averaged across the paracetamol absorption test period. MEASUREMENTS AND RESULTS: Eight patients were classified as feed-intolerant (nTOL) and 15 as feed-tolerant (TOL) [median gastric residual volumes 321% (261-495) and 4% (0-6), respectively]. Gastric emptying was delayed in the feed-intolerant group as assessed by all paracetamol absorption test parameters ( p< or =0.01). The median serum amylin concentration was significantly higher in the feed-intolerant group [nTOL 47.0 (37.7-54.8) versus TOL 22.7 (13.6-26.7) pmol/l, p<0.0001]. A positive correlation between serum amylin and insulin was observed ( r=0.46, p=0.02) but not between amylin and glucose ( r=0.25, p=0.23). CONCLUSIONS: The use of gastric residual volumes to define feed intolerance is justified in critically ill children. High serum amylin levels are associated with delayed gastric emptying in these patients. The correlation between serum amylin and insulin levels indicates a degree of preservation of pancreatic hormonal co-release.     

The effect of acidified enteral feeds on gastric colonization in critically ill patients: results of a multicenter randomized trial. Canadian Critical Care Trials Group

OBJECTIVE: To evaluate the effect of acidified enteral feeds on gastric colonization in critically ill patients compared with a standard feeding formula. DESIGN: Randomized, double-blind, multicenter trial. SETTING: Eight mixed intensive care units at tertiary care hospitals. PATIENTS: We recruited mechanically ventilated critically ill patients expected to remain ventilated for >48 hrs. We excluded patients with gastrointestinal bleeding, acidemia, and renal failure requiring dialysis. We enrolled 120 patients; 38% were female, age (mean +/- SD) was 57.6+/-19.3 yrs, and Acute Physiology and Chronic Health Evaluation II score (mean +/- SD) was 21.6+/-7.6. INTERVENTIONS: Vital High Nitrogen (Abbott Laboratories, Ross Products Division, Columbus, OH) was used as the standard feeding formula for the control group (pH = 6.5). Hydrochloric acid was added to Vital High Nitrogen to achieve a pH of 3.5 in the experimental group. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was gastric colonization. Secondary outcomes included gastric pH, pneumonia, and mortality. The mean gastric pH in patients receiving acid feeds was lower (pH = 3.3) compared with controls (pH = 4.6; p<.05). One patient (2%) on acid feeds was colonized in the stomach with pathogenic bacteria, compared with 20 patients (43%) in the control group (p<.001). There was no difference in the incidence of pneumonia (6.1% in the acid feeds group vs. 15% in the control group; p = .19). Overall, there were 15 deaths in the acid feeds group and seven in the control group (p = .10); four patients in the acid feeds group and three in the control group died during the study period (p not significant). CONCLUSIONS: Acidified enteral feeds preserve gastric acidity and substantially reduce gastric colonization in critically ill patients. Larger studies are needed to examine its effect on ventilator-associated pneumonia and mortality.