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    Marianne Chapman

    To determine the effect of calorie delivery on hospital mortality among critically ill adults receiving enteral nutrition (EN). Secondary outcomes included the effect of calorie delivery on intensive care unit and hospital length of stay... more
    To determine the effect of calorie delivery on hospital mortality among critically ill adults receiving enteral nutrition (EN). Secondary outcomes included the effect of calorie delivery on intensive care unit and hospital length of stay (LOS), duration of mechanical ventilation (MV) and incidence of new-onset pneumonia. We identified randomised clinical trials of EN, with or without supplemental parenteral nutrition (PN), involving adult ICU patients for whom mortality data were available, and when there was a significant difference in calorie supplementation between intervention arms (P < 0.05). We searched English language electronic databases (1946-2014), bibliographies of nutrition society guidelines and high-impact nutrition and critical care journals. We calculated summary odds ratio (OR) estimates and 95% confidence intervals using a random effects estimator, and used meta-regression to assess the effect on mortality of average calories delivered. Of 1545 articles identif...
    Background The appropriate caloric goal for critically ill adults is unclear. We evaluated the effect of restriction of nonprotein calories (permissive underfeeding), as compared with standard enteral feeding, on 90-day mortality among... more
    Background The appropriate caloric goal for critically ill adults is unclear. We evaluated the effect of restriction of nonprotein calories (permissive underfeeding), as compared with standard enteral feeding, on 90-day mortality among critically ill adults, with maintenance of the full recommended amount of protein in both groups. Methods At seven centers, we randomly assigned 894 critically ill adults with a medical, surgical, or trauma admission category to permissive underfeeding (40 to 60% of calculated caloric requirements) or standard enteral feeding (70 to 100%) for up to 14 days while maintaining a similar protein intake in the two groups. The primary outcome was 90-day mortality. Results Baseline characteristics were similar in the two groups; 96.8% of the patients were receiving mechanical ventilation. During the intervention period, the permissive-underfeeding group received fewer mean (±SD) calories than did the standard-feeding group (835±297 kcal per day vs. 1299±467 ...
    Dysphagia is often a comorbidity in patients who require a tracheostomy, yet little is known about patterns of oral intake commencement in tracheostomized patients, or how patterns may vary depending on the clinical population and/or... more
    Dysphagia is often a comorbidity in patients who require a tracheostomy, yet little is known about patterns of oral intake commencement in tracheostomized patients, or how patterns may vary depending on the clinical population and/or reason for tracheostomy insertion. To document patterns of clinical management around the commencement of oral intake throughout hospital admission and along the decannulation pathway in patients with a new tracheostomy, and to examine the nature of variability across multiple clinical populations. A 12-month retrospective review of 126 patients who had undergone an acute tracheostomy was conducted. Within the cohort, patients were further classified into eight clinical populations representing specialty areas within the tertiary referral centre. Data were collected on timing of milestones and patterns of clinical management related to oral and enteral feeding and decannulation. Relationships between temporal variables were calculated, in addition to descriptive analysis of the overall cohort and by clinical population. Median temporal markers of patient progression post-tracheostomy insertion for the cohort were: continuous cuff deflation after 7.5 days, commencement of oral intake after 10.5 days, decannulation after 15 days and cessation of enteral nutrition (EN) after 17 days. However, considerable individual variation and differences between clinical populations was observed. Overall, 86% of the cohort returned to oral intake, although 25% were discharged with EN via a gastrostomy. A total of 86% of the group were decannulated by hospital discharge. Oral intake was introduced at every stage of the decannulation pathway, including prior to cuff deflation, but the majority of patients commenced diet/fluids following cuff deflation or with an uncuffed tube in situ, and most patients who ceased EN did so following decannulation. Commencement of oral intake was evenly split between the intensive care unit (ICU) and the wards. Increased time to commencement of oral intake correlated with increased time to decannulation (r = .805, p = .001), and increased time to decannulation correlated with increased hospital length of stay (r = .687, p = .006). Whilst cohort patterns were observed within the heterogeneous group, sub-analysis revealed distinct patterns of oral intake management across the different clinical populations. The data provide benchmarks enabling comparison by overall cohort as well as by specialist clinical populations, each with differing reasons for tracheostomy insertion. The data would suggest that tracheostomy patients should not be looked upon as a singular cohort; rather, evaluation of factors with specific attention made to underlying aetiology and individual clinical presentation is essential.
    Tracheostomy cuff deflation is a necessary stage of the decannulation pathway, yet the optimal clinical indicators to guide successful cuff deflation are unknown. The study aims were to identify (1) the proportion of patients tolerating... more
    Tracheostomy cuff deflation is a necessary stage of the decannulation pathway, yet the optimal clinical indicators to guide successful cuff deflation are unknown. The study aims were to identify (1) the proportion of patients tolerating continuous cuff deflation at first attempt; (2) the clinical observations associated with cuff deflation success or failure, including volume of above cuff secretions and (3) the predictive capacity of these observations within a heterogeneous cohort. A retrospective review of 113 acutely tracheostomised patients with a subglottic suction tube in situ was conducted. Ninety-five percent of patients (n=107) achieved continuous cuff deflation on the first attempt. The clinical observations recorded as present in the 24h preceding cuff deflation included: (1) medical stability, (2) respiratory stability, (3) fraction of inspired oxygen ≤0.4, (4) tracheal suction ≤1-2 hourly, (5) sputum thin and easy to suction, (6) sputum clear or white, (7) ≥moderate cough strength, (8) above cuff secretions ≤1ml per hour and (9) alertness≥eyes open to voice. Using the presence of all 9 indicators as predictors of successful cuff deflation tolerance, specificity and positive predictive value were 100%, although sensitivity was only 77% and negative predictive value 19%. Refinement to a set of 3 clinically driven criteria (medical and respiratory stability, above cuff secretions ≤1ml/h) provided high specificity (100%), sensitivity (95%), positive predictive value (100%) and an improved negative predictive value (55%). Key criteria can help guide clinical decision-making on patient readiness for cuff deflation.
    Advancements in tracheostomy tube design now provide clinicians with a range of options to facilitate communication for individuals receiving ventilator assistance through a cuffed tube. Little is known about the impact of these modern... more
    Advancements in tracheostomy tube design now provide clinicians with a range of options to facilitate communication for individuals receiving ventilator assistance through a cuffed tube. Little is known about the impact of these modern design features on resistance to air flow. We undertook a bench model test to measure pressure-flow characteristics and resistance of a range of tubes of similar outer diameter, including those enabling subglottic suction and speech. A constant inspiratory ± expiratory air flow was generated at increasing flows up to 150 L/min through each tube (with or without optional, mandatory, or interchangeable inner cannula). Driving pressures were measured, and resistance was calculated (cm H2O/L/s). Pressures changed with increasing flow (P < .001) and tube type (P < .001), with differing patterns of pressure change according to the type of tube (P < .001) and direction of air flow. The single-lumen reference tube encountered the lowest inspiratory a...
    In healthy individuals, both insulin and glucagon-like peptide 1 (GLP-1) are secreted in a pulsatile fashion. Insulin has greater glucose-lowering properties when administered in pulses compared with a constant i.v. infusion. The primary... more
    In healthy individuals, both insulin and glucagon-like peptide 1 (GLP-1) are secreted in a pulsatile fashion. Insulin has greater glucose-lowering properties when administered in pulses compared with a constant i.v. infusion. The primary aim of this randomised double-dummy cross-over study was to compare the insulinotropic response to pulsatile and continuous i.v. infusions of equivalent doses of GLP-1. Twelve healthy participants aged 18-35 years were randomised to three different treatments on separate days: a continuous infusion day (GLP-1 at 0.6 pmol kg(-1) min(-1) [1 ml/min] and a 1 ml placebo bolus every 6 min); a pulsatile infusion day (placebo at 1 ml/min and a 3.6 pmol/kg GLP-1 bolus every 6 min); and a placebo day (placebo at 1 ml/min and a 1 ml placebo bolus every 6 min). Between 45 and 120 min, a hyperglycaemic clamp was used to maintain blood glucose at 9 mmol/l. Venous blood glucose and plasma insulin concentrations were measured every 5 min from 0 to 45 min and every 1 min from 45 to 120 min; plasma glucagon was measured every 15 min. The order of treatment was randomised by the Pharmacy Department and both study investigators and participants were blinded to the treatment arm. The dextrose requirement and glucagon data were analysed using repeated measures ANOVA and insulin data were analysed with a linear mixed effects maximum likelihood model. Continuous and pulsatile infusions of GLP-1 increased the dextrose requirement by ~threefold (p < 0.001) and increased insulin secretion by ~ninefold (p < 0.001). There was no difference in the effect of both treatments. Although hyperglycaemia reduced plasma glucagon concentrations, there was no difference between the treatment days. In healthy individuals, pulsatile and continuous administration of i.v. GLP-1 appears to have comparable insulinotropic effects. ACTRN12612001040853 FUNDING: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia.
    Critical illness following head injury is associated with a hypermetabolic state but there are insufficient epidemiological data describing acute nutrition delivery to this group of patients. Furthermore, there is little information... more
    Critical illness following head injury is associated with a hypermetabolic state but there are insufficient epidemiological data describing acute nutrition delivery to this group of patients. Furthermore, there is little information describing relationships between nutrition and clinical outcomes in this population. We undertook an analysis of observational data, collected prospectively as part of International Nutrition Surveys 2007-2013, and extracted data obtained from critically ill patients with head trauma. Our objective was to describe global nutrition support practices in the first 12 days of hospital admission after head trauma, and to explore relationships between energy and protein intake and clinical outcomes. Data are presented as mean (SD), median (IQR), or percentages. Data for 1045 patients from 341 ICUs were analyzed. The age of patients was 44.5 (19.7) years, 78 % were male, and median ICU length of stay was 13.1 (IQR 7.9-21.6) days. Most patients (94 %) were enterally fed but received only 58 % of estimated energy and 53 % of estimated protein requirements. Patients from an ICU with a feeding protocol had greater energy and protein intakes (p <0.001, 0.002 respectively) and were more likely to survive (OR 0.65; 95 % CI 0.42-0.99; p = 0.043) than those without. Energy or protein intakes were not associated with mortality. However, a greater energy and protein deficit was associated with longer times until discharge alive from both ICU and hospital (all p <0.001). Nutritional deficits are commonplace in critically ill head-injured patients and these deficits are associated with a delay to discharge alive.
    To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. Intensive care units of 18 Australian and New Zealand hospitals: March 2001.... more
    To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. Intensive care units of 18 Australian and New Zealand hospitals: March 2001. Prospective, observational, multicentre study. All admissions to participating intensive care units were screened and all patients who received a transfusion of RBC were enrolled. The indications for transfusion were recorded and compared with Australian National Health and Medical Research Council guidelines. Transfusions conforming to these guidelines were deemed appropriate. RBC transfusion in intensive care and transfusion appropriateness. 1808 admissions to intensive care units were screened: 357 (19.8%) admissions (350 patients) received an RBC transfusion while in intensive care. Overall, 1464 RBC units were administered in intensive care on 576 transfusion days. The most common indications for transfusion were acute bleeding (60.1%; 880/1464) and diminished physiological reserve (28.9%; 423/1464). The rate of inappropriate transfusion was 3.0% (44/1464). Diminished physiological reserve with haemogloblin level > or = 100 g/L was the indication in 50% (22/44) of inappropriate transfusions; no indication was provided for 31% (15/44). The rate of inappropriate transfusion in Australian and New Zealand intensive care units in 2001 was remarkably low.
    ABSTRACT
    Background Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large... more
    Background Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large randomised controlled trial, and use of dopamine remains controversial. We have done a multicentre, randomised, double-blind, placebo-controlled study of low-dose dopamine in patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction (oliguria or increase in serum creatinine concentration). Methods 328 patients admitted to 23 participating intensive-care units (ICUs) were randomly assigned a continuous intravenous infusion of tow-dose dopamine (2 mug kg(-1) min(-1)) or placebo administered through a central venous catheter while in the ICU. The primary endpoint was the peak serum creatinine concentration during the infusion. Analyses excluded four patients with major protocol violation...
    Corticosteroid-binding globulin (CBG) is cleaved by neutrophil elastase converting the high-affinity (haCBG) conformation of CBG to a low-affinity (laCBG) conformation with a ninefold reduced cortisol-binding affinity. These in vitro data... more
    Corticosteroid-binding globulin (CBG) is cleaved by neutrophil elastase converting the high-affinity (haCBG) conformation of CBG to a low-affinity (laCBG) conformation with a ninefold reduced cortisol-binding affinity. These in vitro data suggest that cortisol release by CBG cleavage results in the targeted delivery of cortisol to areas of inflammation. Our objective was to determine whether CBG cleavage alters circulating levels of haCBG and laCBG in vivo in proportion to sepsis severity. Prospective, observational cohort study in an adult tertiary level Intensive Care Unit in Adelaide, Australia. Thirty-three patients with sepsis or septic shock grouped by illness severity [sepsis, septic shock survivors, septic shock nonsurvivors and other shock]. Plasma levels of haCBG and laCBG were assessed using a recently developed in-house assay in patients. Plasma total and free cortisol levels were also measured. Plasma total CBG and haCBG levels fell significantly, in proportion to disea...
    The aim of this study was to explore the degree and determinants of satisfaction of family members of patients being cared for in an Australasian intensive care unit. This was a prospective observational study that took place within a... more
    The aim of this study was to explore the degree and determinants of satisfaction of family members of patients being cared for in an Australasian intensive care unit. This was a prospective observational study that took place within a mixed medical/surgical, level three intensive care unit. One hundred and eight family members of patients staying in the intensive care for more than 48 hours were identified. Eight were excluded because next of kin contact details were unavailable. A questionnaire was posted to next of kin four weeks after intensive care unit discharge. Subjects who had not responded after four weeks were contacted by telephone and, if consent was given, a phone questionnaire was performed. Evidence of family meetings with the social worker or medical staff was sought in the patients' case notes retrospectively. Family satisfaction was measured using a 10-item questionnaire incorporating visual analogue scales. Seven subjects refused to participate. Fifty-nine res...
    To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. Intensive care units of 18 Australian and New Zealand hospitals: March 2001.... more
    To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. Intensive care units of 18 Australian and New Zealand hospitals: March 2001. Prospective, observational, multicentre study. All admissions to participating intensive care units were screened and all patients who received a transfusion of RBC were enrolled. The indications for transfusion were recorded and compared with Australian National Health and Medical Research Council guidelines. Transfusions conforming to these guidelines were deemed appropriate. RBC transfusion in intensive care and transfusion appropriateness. 1808 admissions to intensive care units were screened: 357 (19.8%) admissions (350 patients) received an RBC transfusion while in intensive care. Overall, 1464 RBC units were administered in intensive care on 576 transfusion days. The most common indications for transfusion were acute bleeding (60.1%; 880/146...
    To determine functional outcomes 6 months after intensive care unit admission for severe infection due to pandemic (H1N1) 2009 influenza and examine the relationship between nutrition during ICU admission and outcome. Retrospective cohort... more
    To determine functional outcomes 6 months after intensive care unit admission for severe infection due to pandemic (H1N1) 2009 influenza and examine the relationship between nutrition during ICU admission and outcome. Retrospective cohort study of patients with confirmed H1N1 influenza admitted to the ICU, Royal Adelaide Hospital, South Australia, June- October 2009. Data were collected from medical records, dietitian notes and the daily ICU chart and included: demographics, daily kilocalories (Kcal) and protein delivered compared with dietitian-calculated requirement, ICU and hospital length of stay. Weight change and functional outcome at 6 months were determined prospectively by telephone interview using the 12-Item Short Form Health Survey and the EuroQol Group 5-Dimension Questionnaire. Of 25 patients with H1N1 infection, 23 were included in the study (14 men; median age, 48 years (interquartile range [IQR], 39-55 years); median Acute Physiology and Chronic Health Evaluation (A...
    During critical illness, enteral nutrition remains central to clinical care and an understanding of gut dysfunction is therefore important. Contemporary data have contributed to our knowledge in this area and this review will concentrate... more
    During critical illness, enteral nutrition remains central to clinical care and an understanding of gut dysfunction is therefore important. Contemporary data have contributed to our knowledge in this area and this review will concentrate on recently published studies. It is difficult to precisely measure gastric emptying and nutrient absorption as part of routine clinical care. However, techniques for the measurement of these parameters for research purposes have been refined, studied and validated. These methodologies allow the evaluation of novel treatments that modulate gastric emptying. Quantification and an understanding of the mechanisms of nutrient malabsorption may facilitate the development of therapeutic agents to improve absorption and/or formulae, which are more readily absorbed, thereby improving nutritional and clinical outcomes. Improved understanding of gut pathophysiology in critical illness provides opportunities for the development and testing of novel and targeted treatment strategies, with the objective to improve clinical outcomes in this group.
    Objective: To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. Setting: Intensive care units of 18 Australian and New Zealand... more
    Objective: To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. Setting: Intensive care units of 18 Australian and New Zealand hospitals: March 2001. Design: Prospective, observational, multicentre study. Methods: All admissions to participating intensive care units were screened and all patients who received a transfusion
    There is a high risk of post-traumatic stress disorder (PTSD) in relatives of intensive care unit (ICU) patients. To determine the prevalence and predictors of symptoms of PTSD in relatives of an Australian critically ill population. 108... more
    There is a high risk of post-traumatic stress disorder (PTSD) in relatives of intensive care unit (ICU) patients. To determine the prevalence and predictors of symptoms of PTSD in relatives of an Australian critically ill population. 108 consecutive patients staying >48 h in a mixed, level three ICU were identified. On day three of admission, their next-of-kin were contacted and consent obtained for a telephonic questionnaire to be done at 90 days after ICU discharge. This consisted of the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised (IES-R) questionnaires administered to relatives at 90 days post-discharge from the ICU. An IES-R score of >26 was used to define PTSD symptoms. Eight subjects were excluded because the next-of-kin details were unavailable. 37 other subjects refused to participate. Out of a total of 108, 63 family members were included, including 49 next-of-kin of patients who survived. The prevalence of PTSD symptoms was 41.2% (26/6...
    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... more
    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. 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 ar...
    Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large randomised... more
    Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large randomised controlled trial, and use of dopamine remains controversial. We have done a multicentre, randomised, double-blind, placebo-controlled study of low-dose dopamine in patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction (oliguria or increase in serum creatinine concentration). 328 patients admitted to 23 participating intensive-care units (ICUs) were randomly assigned a continuous intravenous infusion of low-dose dopamine (2 microg kg(-1) min(-1)) or placebo administered through a central venous catheter while in the ICU. The primary endpoint was the peak serum creatinine concentration during the infusion. Analyses excluded four patients with major protocol violations. The groups assigned dopamine (n=161) and placebo (n=163) were similar in terms of baseline characteristics, renal function, and duration of trial infusion. There was no difference between the dopamine and placebo groups in peak serum creatinine concentration during treatment (245 [SD 144] vs 249 [147] micromol/L; p=0.93), in the increase from baseline to highest value during treatment (62 [107] vs 66 [108] micromol/L; p=0.82), or in the numbers of patients whose serum creatinine concentration exceeded 300 micromol/L (56 vs 56; p=0.92) or who required renal replacement therapy (35 vs 40; p=0.55). Durations of ICU stay (13 [14] vs 14 [15] days; p=0.67) and of hospital stay (29 [27] vs 33 [39] days; p=0.29) were also similar. There were 69 deaths in the dopamine group and 66 in the placebo group. Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction.
    Gastrointestinal dysmotility is a common feature of critical illness, with a number of significant implications that include malnutrition secondary to reduced feed tolerance and absorption, reflux and aspiration resulting in reduced lung... more
    Gastrointestinal dysmotility is a common feature of critical illness, with a number of significant implications that include malnutrition secondary to reduced feed tolerance and absorption, reflux and aspiration resulting in reduced lung function and ventilator-associated pneumonia, bacterial overgrowth and possible translocation causing nosocomial sepsis. Prokinetic agent administration can improve gastric emptying and caloric delivery, but its effect on nutrient absorption and clinical outcomes is, as yet, unclear. Postpyloric delivery of nutrition has not yet been demonstrated to increase caloric intake or improve clinical outcomes.
    Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish... more
    Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ⋅ min), as a continuous 24-h infusion ("prolonged"), two 4.5-h infusions separated by 20 h…
    To highlight the recent developments in nutritional support for critically ill patients. Increasing data support the benefits of early initiation of enteral nutrition, with improvements in small intestinal absorption and clinical... more
    To highlight the recent developments in nutritional support for critically ill patients. Increasing data support the benefits of early initiation of enteral nutrition, with improvements in small intestinal absorption and clinical outcomes. In contrast to the previous belief, recent data suggest caloric administration of greater than 65-70% of daily requirement is associated with poorer clinical outcomes, especially when supplemental parenteral nutrition is used to increase the amount of caloric delivery. The role of supplementary micronutrients and anti-inflammatory lipids has been further evaluated but remains inconclusive, and is not currently recommended. Together, current findings indicate that intragastric enteral nutrition should be initiated within 24 h of admission to ICU and supplementary parenteral nutrition should be avoided. Future research should aim to clarify the optimal energy delivery for best clinical outcomes, and the role of small intestinal function and its flora in nutritional care and clinical outcomes.
    Gastrointestinal dysmotility and dysfunction underlie our difficulties in providing adequate nutrition by the enteral route to our critically ill patients. Recent studies have quantified gastric emptying and nutrient absorption. Slow... more
    Gastrointestinal dysmotility and dysfunction underlie our difficulties in providing adequate nutrition by the enteral route to our critically ill patients. Recent studies have quantified gastric emptying and nutrient absorption. Slow gastric emptying is common and probably mediated by cholecystokinin and reduced active ghrelin concentrations. The cause of impaired nutrient absorption is not yet fully understood but may be related to small intestinal blood flow and/or mucosal factors. The absorption of the different macronutrients may be affected in different ways both by critical illness and by therapies. A better understanding of this may optimize the design of nutrient formulations in the future. New treatment modalities for gastrointestinal dysfunction are being investigated and include small intestinal feeding, nonpharmacological options such as acupuncture, and drugs including novel motilin receptor agonists, and opioid antagonists. We are gradually developing a better understanding of how the gut works during critical illness, which has implications for optimizing the delivery of nutrition and thereby improving nutritional and clinical outcomes.
    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. Prospective, double-blind, randomized, and... more
    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. Prospective, double-blind, randomized, and placebo-controlled trial. General intensive care unit in a university hospital. 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). 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. 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). 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.
    Although enteral nutrition is standard care for critically ill patients, nutrient absorption has not been quantified in this group and may be impaired due to intestinal dysmotility. The objectives of this study were to measure small... more
    Although enteral nutrition is standard care for critically ill patients, nutrient absorption has not been quantified in this group and may be impaired due to intestinal dysmotility. The objectives of this study were to measure small intestinal glucose absorption and duodenocecal transit and determine their relationship with glycemia in the critically ill. Prospective observational study of healthy and critically ill subjects. Tertiary mixed medical-surgical adult intensive care unit. Twenty-eight critically ill patients and 16 healthy subjects were studied. MATERIALS AND MAIN RESULTS: Liquid feed (100 kcal/100 mL), labeled with Tc-sulfur colloid and including 3 g of 3-O-methylglucose, was infused into the duodenum. Glucose absorption and duodenocecal transit were measured using the area under the 3-O-methylglucose concentration curve and scintigraphy, respectively. Data are median (range). Glucose absorption was reduced in critical illness when compared to health (area under the concentration curve: 16 [1-32] vs. 20 [14-34] mmol/L·min; p = .03). Small intestinal transit times were comparable in patients and healthy subjects (192 [9-240] vs. 168 [6-240] min; p = .99) and were not related to glucose absorption. Despite higher fasting blood glucose concentrations (6.3 [5.1-9.3] vs. 5.7 [4.6-7.6] mmol/L; p < .05), the increment in blood glucose was sustained for longer in the critically ill (Δ glucose at t = 60; 1.9 [-2.1-5.0] mmol/L vs. -0.2 [-1.3-2.3] mmol/L; p < .01). Critical illness is associated with reduced small intestinal glucose absorption, but despite this, the glycemic response to enteral nutrient is sustained for longer.
    Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by... more
    Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice. Prospective observational study in humans and mice. ICU and university-affiliated research laboratory. Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied. Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection. Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcripts were reduced by 55% (p…
    ABSTRACT
    To formally document the effectiveness of tegaserod as a prokinetic agent in intensive care patients. The audit was designed in consultation with the Northern Territory Drug and Therapeutics Committee. Tegaserod was added to the feeding... more
    To formally document the effectiveness of tegaserod as a prokinetic agent in intensive care patients. The audit was designed in consultation with the Northern Territory Drug and Therapeutics Committee. Tegaserod was added to the feeding protocol and prokinetic algorithm in the ICU, and a prospective audit was performed of patients receiving the medication between May and September 2006. Over the 5-month period, 40 patients received tegaserod after failing to respond to two doses of metoclopramide. Median daily volume of gastric aspirate was reduced from 1220mL in the 24 hours before tegaserod to 887.5mL in the first 24 hours after its introduction, and to 280mL in the second 24 hours (P=0.01 and P<0.001, respectively). Tegaserod was an effective prokinetic agent in 85% (34) patients. Attributable diarrhoea occurred in 13% (5) patients, but did not require intervention. Tegaserod is an effective alternative prokinetic agent for ICU patients with a safer side-effect profile. We believe it warrants further investigation.
    Hyperglycaemia occurs frequently in the critically ill, affects outcome adversely, and is exacerbated by enteral feeding. Furthermore, treatment with insulin in this group is frequently complicated by hypoglycaemia. In healthy patients... more
    Hyperglycaemia occurs frequently in the critically ill, affects outcome adversely, and is exacerbated by enteral feeding. Furthermore, treatment with insulin in this group is frequently complicated by hypoglycaemia. In healthy patients and those with type 2 diabetes, exogenous glucagon-like peptide-1 (GLP-1) decreases blood glucose by suppressing glucagon, stimulating insulin and slowing gastric emptying. Because the former effects are glucose-dependent, the use of GLP-1 is not associated with hypoglycaemia. The objective of this study was to establish if exogenous GLP-1 attenuates the glycaemic response to enteral nutrition in patients with critical illness induced hyperglycaemia. Seven mechanically ventilated critically ill patients, not previously known to have diabetes, received two intravenous infusions of GLP-1 (1.2 pmol/kg/min) and placebo (4% albumin) over 270 minutes. Infusions were administered on consecutive days in a randomised, double-blind fashion. On both days a mixed...
    Delay in initiating enteral nutrition has been reported to disrupt intestinal mucosal integrity in animals and to prolong the duration of mechanical ventilation in humans. However, its impact on intestinal absorptive function in... more
    Delay in initiating enteral nutrition has been reported to disrupt intestinal mucosal integrity in animals and to prolong the duration of mechanical ventilation in humans. However, its impact on intestinal absorptive function in critically ill patients is unknown. The aim of this study was to examine the impact of delayed enteral nutrition on small intestinal absorption of 3-O-methyl-glucose. Prospective, randomized study. Tertiary critical care unit. Studies were performed in 28 critically ill patients. Patients were randomized to either enteral nutrition within 24 hrs of admission (14 "early feeding": 8 males, 6 females, age 54.9 ± 3.3 yrs) or no enteral nutrition during the first 4 days of admission (14 "delayed feeding": 10 males, 4 females, age 56.1 ± 4.2 yrs). Gastric emptying (scintigraphy, 100 mL of Ensure (Abbott Australia, Kurnell, Australia) with 20 MBq Tc-suphur colloid), intestinal absorption of glucose (3 g of 3-O-methyl-glucose), and clinical outco...
    Enteral feed intolerance occurs frequently in critically ill patients and can be associated with adverse outcomes. "Energy-dense formulae" (ie, >1 kcal/mL) are often prescribed to critically ill patients to reduce... more
    Enteral feed intolerance occurs frequently in critically ill patients and can be associated with adverse outcomes. "Energy-dense formulae" (ie, >1 kcal/mL) are often prescribed to critically ill patients to reduce administered volume and are presumed to maintain or increase calorie delivery. The aim of this study was to compare gastric emptying of standard and energy-dense formulae in critically ill patients. In a retrospective comparison of 2 studies, data were analyzed from 2 groups of patients that received a radiolabeled 100-mL "meal" containing either standard calories (1 kcal/mL) or concentrated calories (energy-dense formulae; 2 kcal/mL). Gastric emptying was measured using a scintigraphic technique. Radioisotope data were collected for 4 hours and gastric emptying quantified. Data are presented as mean ± SE or median [interquartile range] as appropriate. Forty patients were studied (n = 18, energy-dense formulae; n = 22, standard). Groups were well mat...
    To determine the response of the proximal stomach to small intestinal nutrients in critically ill patients. Proximal gastric motility was measured in 13 critically ill patients (49.3 +/- 4.7 years) and 12 healthy volunteers (27.7 +/- 2.9... more
    To determine the response of the proximal stomach to small intestinal nutrients in critically ill patients. Proximal gastric motility was measured in 13 critically ill patients (49.3 +/- 4.7 years) and 12 healthy volunteers (27.7 +/- 2.9 years) using a barostat technique. Recordings were performed at baseline, during a 60-min intra-duodenal infusion of Ensure (2 kcal/min), and for 2 h following the infusion. Minimum distending pressure (MDP), intra-bag volume and fundic wave activity were determined. The MDP was higher in patients (11.7 +/- 1.1 vs 7.8 +/- 0.7 mmHg; P < 0.01). Baseline intra-bag volumes were similar in the 2 groups. In healthy subjects, a 'bimodal' proximal gastric volume response was observed. In patients, the initial increase in proximal gastric volume was small and delayed, but eventually reached a maximal volume similar to that of healthy subjects. In healthy subjects, the proximal gastric volume rapidly returned to baseline level after nutrient infusi...

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