Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study

Introduction  

Delayed gastric emptying and feed intolerance occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to determine fasting and nutrient-stimulated plasma PYY concentrations and their relationship to cholecystokinin (CCK) in critically ill patients.     

The relationship between gastric emptying,plasma cholecystokinin,and peptide YY in critically ill patients

Background  

Cholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness.     

Gastrointestinal motility and prokinetics in the critically ill

PURPOSE OF REVIEW: Enteral nutrition is frequently unsuccessful in the critically ill due to gastrointestinal dysfunction. Current treatment strategies are often disappointing. In this article upper gastrointestinal function in health together with abnormalities seen during critical illness are reviewed, and potential therapeutic options summarized. RECENT FINDINGS: Reflux oesophagitis occurs frequently due to reduced or absent lower oesophageal sphincter tone. In the stomach a number of motor patterns contribute to slow gastric emptying. The fundus has reduced compliance, there are less frequent contractions in both the proximal and distal stomach, isolated pyloric activity is increased and the organization of duodenal motor activity is abnormal. In response to nutrients, enterogastric feedback is enhanced, fundic relaxation and subsequent recovery is delayed, antral motility is further reduced and localized pyloric contractions stimulated. Elevated concentrations of hormones such as cholecystokinin and peptide YY are potential mediators for these phenomena. Rapid tachyphylaxis occurs with the commonly used prokinetics, metoclopramide and erythromycin, and novel agents are under investigation. Independent of gastric emptying, nutrient absorption is reduced. SUMMARY: There has been considerable progress in understanding the pathogenesis of mechanisms causing feed intolerance in critical illness, but this is yet to be translated into therapeutic benefit.     

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.     

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.     

Gastric emptying in mechanically ventilated critically ill patients: effect of neuromuscular blocking agent

Objective To assess gastrointestinal function in critically ill patients receiving muscle relaxant and to test clinical tolerance to enteral nutrition.Design and setting Prospective study in an intensive care unit.Patients 20 critically ill patients requiring sedation with muscle relaxant to obtain adequate mechanical ventilation.Measurements and results Patients were randomly selected to receive infusions of opioid sedation during the first session (session 1) and the same sedation with muscle relaxation (cisatracurium) during the second session (session 2). Gastric emptying was assessed by the paracetamol absorption technique. Following the paracetamol absorption 200 ml enteral feed was given, and the residual gastric volume was measured 1 and 2 h after feeding. The maximum plasma concentration (Cmax) was 14 mg/l (range 5–26) when patients received sedation, and 12 mg/l (range 5–30) when they received muscle relaxant. The target time for reaching the maximum plasma concentration (Tmax) was 30 min (range 20–60) and 35 min (range 20–60), respectively, in sessions 1 and 2. There was no significant difference between the two session as regards Tmax, Cmax, or AUC_0–120. The residual volumes were 110±65 ml (H1) and 95±76 ml (H2) during session 1 and 125±85 ml (H1) and 105±90 ml (H2) during session 2.Conclusions Enteral feeding is one of the most effective methods of supporting nutritional needs in the critically ill patient. We conclude that in critically ill patients requiring sedation gastric emptying is not improved by neuromuscular blocking agent.This study was supported by a grant from Charles Nicolle Hospital (98097 HP)     

Labeled acetate to assess intestinal absorption in critically ill patients

OBJECTIVE: To compare the absorption of carbon-13(13C) acetate-enriched nutrients with D-xylose absorption. DESIGN: Prospective cohort observational study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: A total of 24 critically ill patients requiring enteral nutritional support. INTERVENTION: The patients were divided into three groups according to the route of 13C acetate administration: 1) gastric, 2) jejunal, and 3) intravenous. D-xylose was administered via the same route as enteral nutrition. MEASUREMENTS AND MAIN RESULTS: 13C acetate absorption and oxidation were reflected by pulmonary 13CO2 excretion. Breath 13CO2 isotopic enrichment was measured by mass spectrometry. 13C acetate absorption was rapid, and D-xylose absorption was depressed in all three groups, compared with the normal values (p <.0001). Breath CO isotopic enrichment was similar after intravenous and jejunal administration but slightly delayed during the first 240 mins after gastric administration (p <.01). Enteral feeding was well tolerated: mean energy delivery amounted to 77%, 88%, and 86% of measured resting energy expenditure on days 1-3. CONCLUSIONS: Gastric and jejunal 13C acetate are rapidly absorbed in critically ill surgical patients requiring enteral nutrition, contrasting with a depressed or delayed D-xylose absorption. 13CO2 recovery kinetics was similar after jejunal or intravenous 13C acetate and slightly depressed after gastric administration. Further studies are required to determine the value of labeled nutrients to assess gastric emptying and intestinal absorption.     

Glucose absorption and gastric emptying in critical illness

Introduction  

Delayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients.     

Diminished functional association between proximal and distal gastric motility in critically ill patients

OBJECTIVE: This study examined the effects of critical illness on the relationship between proximal and distal gastric motor activity during fasting and duodenal nutrient stimulation. DESIGN: Prospective, case-controlled study. PATIENTS AND PARTICIPANTS: Ten critically ill patients and ten healthy volunteers. INTERVENTIONS: Concurrent proximal gastric (barostat) and antro-pyloro-duodenal (manometry) motility were recorded during fasting and during two 60-min duodenal nutrient infusions (Ensure at 1[Symbol: see text]kcal/min and 2[Symbol: see text]kcal/min) in random order, separated by a 2-h wash-out period. RESULTS: Baseline proximal gastric volumes were similar between the two groups. At 10[Symbol: see text]min nutrient-induced fundic relaxation was lower in patients than healthy subjects (45[Symbol: see text]+/-[Symbol: see text]26 vs. 196[Symbol: see text]+/-[Symbol: see text]29[Symbol: see text]ml). In patients the frequency and volume amplitude of fundic waves were also lower. There were fewer propagated antral waves in patients than in healthy subjects during both fasting and nutrient infusion. These were more retrograde, shorter in length and associated with a pyloric contraction. The proportion of fundic waves followed by a distally propagated antral wave was significantly less in patients (0%, 0-8%) than controls 36% (11-44%). CONCLUSIONS: In critical illness, in addition to impairment of proximal and distal gastric motor activity, the association between the two gastric regions is abnormal. This disturbance may interfere with meal distribution and further contribute to slow gastric emptying in these patients.     

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.     

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.     

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h). Gastric emptying rates were measured by gamma camera scintigraphy of technetium 99m sulfur colloid and plasma CCK levels were measured by a sensitive and specific bioassay. Basal CCK levels averaged 1.0 +/- 0.1 pM (mean +/- SEM, n = 8) and increased to 7.1 +/- 1.1 pM after a mixed liquid meal. After glucose ingestion, but without CCK infusion, CCK levels did not change from basal, and the gastric emptying t1/2 was 68 +/- 3 min. Plasma glucose levels increased from basal levels of 91 +/- 3.9 mg/dl to peak levels of 162 +/- 11 mg/dl and insulin levels increased from 10.7 +/- 1.8 microU/ml to peak levels of 58 +/- 11 microU/ml. After glucose ingestion, with CCK infused at 24 pmol/kg per h, plasma CCK levels increased to 8 pM and the gastric emptying t1/2 increased to 148 +/- 16 min. In concert with this delay in gastric emptying, peak glucose levels rose to only 129 +/- 17 mg% and peak insulin levels rose to only 24.2 +/- 4.2 microU/ml. With CCK at 12 pmol/kg per h, similar but less dramatic changes were seen. To demonstrate that endogenous CCK could modify the plasma glucose and insulin responses to oral glucose, oral glucose was given with 50 g of lipid containing long-chain triglycerides. This lipid increased peak CCK levels to 3.7 +/- 0.9 pM. Concomitant with this rise in CCK was a delay in gastric emptying and a lowering of plasma glucose and insulin values. To confirm that CCK reduced hyperglycemia by its effect on gastric motility, 36 g glucose was perfused directly into the duodenum through a nasal-duodenal feeding tube in four subjects. With duodenal perfusion of glucose, there was no change in plasma CCK levels, but plasma glucose levels increased from basal levels of 93+/-5 to 148+/-6 mg/dl and insulin levels rose from 10.6+/-3.5 to 29.5+/-5.2 microU/ml. When CCK was infused at 24 pmol/kg per h, neither the plasma glucose nor insulin responses to the duodenal administration of glucose were modified. Thus we conclude that CCK, in physiological concentrations, delays gastric emptying, slows the delivery of glucose to the duodenum, and reduces postprandial hyperglycemia. These data indicate, therefore, that CCK has a significant role in regulating glucose homeostasis in human.     

The impact of admission diagnosis on gastric emptying in critically ill patients

Introduction  

Disturbed gastric emptying (GE) occurs commonly in critically ill patients. Admission diagnoses are believed to influence the incidence of delayed GE and subsequent feed intolerance. Although patients with burns and head injury are considered to be at greater risk, the true incidence has not been determined by examination of patient groups of sufficient number. This study aimed to evaluate the impact of admission diagnosis on GE in critically ill patients.     

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.     

Regulation of gastric emptying in humans by cholecystokinin.

In the present study we used a bioassay system for measuring plasma cholecystokinin (CCK) to evaluate whether CCK has a physiologic role in regulating gastric emptying in humans. Plasma CCK levels and gastric emptying after ingestion of a mixed liquid meal were determined in five normal male volunteers. Fasting CCK levels averaged 0.8 +/- 0.1 pM and increased to 6.5 +/- 1.0 pM within 10 min of drinking the mixed meal. CCK levels remained elevated for up to 90 min. Gastric emptying after a meal was slow; at the end of the 90 min 68% of the original volume remained in the stomach. The rate of gastric emptying of water was then measured in the same individuals with a simultaneous infusion of either saline, or one of two doses of CCK (12 pmol/kg per h and 24 pmol/kg per h). With the saline infusion, plasma CCK levels did not increase above basal and gastric contents emptied rapidly. At the end of 90 min only 7% of the original volume remained in the stomach. The lower dose of CCK resulted in a plasma level of 3.4 pM which both reproduced the average postprandial plasma level and caused a significant delay in gastric emptying. The higher dose of CCK achieved plasma levels of 8 pM and resulted in a delay in gastric emptying that was similar to that seen with the mixed meal. Since exogenous CCK at concentrations which occur postprandially delays gastric emptying, we conclude that CCK is a physiologic regulator of gastric emptying.     

Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes

Introduction  

Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes.     

Dobutamine pharmacokinetics and pharmacodynamics in pediatric intensive care patients.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of dobutamine in critically ill children. DESIGN: A prospective study of pediatric patients receiving continuous infusions of dobutamine in a stepwise format from 2.5 to 10.0 micrograms/kg/min. SETTING: A pediatric critical care unit. PATIENTS: Twelve children ranging in age from 1 month to 17 yrs with primary medical conditions. MEASUREMENTS: Plasma dobutamine concentrations and hemodynamic responses were measured at each infusion rate at steady state. Dose response data were analyzed to determine the threshold or minimum plasma dobutamine concentration necessary for discernible hemodynamic effects. MAIN RESULTS: Dobutamine plasma clearance rates ranged from 40 to 130 mL/kg/min. Each patient presented a linear increase in the plasma dobutamine concentration at each infusion rate (r2 = .97, p less than .001). Plasma clearance rate vs. actual dobutamine concentration did not vary. Cardiac output, BP, and heart rate increased 30%, 17%, and 7%, respectively, at maximal dose. The dobutamine concentration thresholds for changes in cardiac output, BP, and heart rate were 13 +/- 6, 23 +/- 14, and 65 +/- 30 ng/mL, respectively. CONCLUSIONS: There was no effect of plasma dobutamine concentration or infusion rate on plasma clearance rate. For this group of patients, over the range of the intravenous doses studied, dobutamine pharmacokinetics followed a first-order kinetic model. Threshold values for dobutamine usually show increases in cardiac output before changes in heart rate. These data demonstrate that dobutamine is an effective inotropic agent in critically ill pediatric patients and has minimal chronotropic action.     

Nutrition support in the critically ill patient

Despite an absence of well-controlled studies demonstrating a clear mortality benefit, providing nutrition support in the critically ill patient has become routine in most ICU settings. Unless clearly contraindicated, patients should be fed enterally, using conventional isotonic feedings employing gastric or postpyloric access. When to begin nutrition support varies, depending on baseline nutritional status, anticipated time until oral feedings are resumed, and the degree of stress. Energy and protein requirements should be assessed routinely with minimum goals of avoiding overfeeding and minimizing any net negative nitrogen balance. All patients receiving feedings require close surveillance to identify predictable complications and to tailor therapy to achieve nutritional goals. Adjunctive therapies should be employed as needed to help achieve nutritional goals, eg, insulin infusions to control serum glucose and prokinetic agents to improve gastric emptying. When feasible and safe, parenterally fed patients should be transitioned to enteral or oral feedings when appropriate.